Bicyclic fused heteroaromatic ring derivative, and pharmaceutical composition and use thereof

Abstract

Provided in the present application is a bifunctional compound as shown in formula (I). In addition, further disclosed in the present application are a pharmaceutically acceptable salt or a stereoisomer, a pharmaceutical composition and the use of the compound. The compound of the present application has a good degradation effect on EED, has a good inhibition effect on cell proliferation of tumor cells, and has a potential treatment effect on tumors. POI—(L)n0—ULM (I)

Description

This application claims priorities to Chinese Patent Application No. 202311789109.3, titled “BICYCLIC FUSED HETEROAROMATIC RING DERIVATIVE, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF” filed before the China National Intellectual Property Administration on December 22, 2023, and Chinese Patent Application No. 202410735064.X, titled “BICYCLIC FUSED HETEROAROMATIC RING DERIVATIVE, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF” filed before the China National Intellectual Property Administration on June 6, 2024, which are incorporated herein by reference in their entireties. TECHNICAL FIELD The present application relates to the field of pharmaceutical technology, and in particular, to a bicyclic fused heteroaromatic ring derivative, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a pharmaceutical composition thereof, and medical uses thereof. BACKGROUND The Polycomb group (PcG) protein Polycomb repressive complex 2 (PRC2) performs a core function of transcriptional repression in an organism, achieving gene silencing by catalyzing trimethylation of histone H3 at lysine 27 (H3K27me3). It can promote tumor initiation and progression by inhibiting the expression of tumor suppressor genes in tumors. The catalytic subunit of PRC2, EZH2, is an important representative of third-generation epigenetic regulation precision therapeutic targets. Compared to first-generation and second-generation pan-epigenetic regulation targets, current therapeutic targets can target tumors with specific mutation types, offering significantly improved efficacy and safety. Although EZH2 is an ideal target for directly shutting down aberrant PRC2 activity, PRC2 functions as a protein complex, whose activity and functionality are highly dependent on the regulatory role of the scaffold and another core subunit, EED. Interfering with the protein-protein interaction (PPI) between EZH2 and EED can also inhibit the methyltransferase activity of the PRC2 complex. Novartis AG pioneered the demonstration through high-throughput screening that the H3K27me3 recognition pocket of EED is “druggable”, and discovered that targeting EED can allosterically inhibit the catalytic activity of EZH2. The rise of targeted protein degradation (TPD) technology has provided a new pathway for small molecule drug development. Among these, proteolysis targeting chimeras (PROTACs) are the most well-developed system. Their mechanism of action involves linking a small molecule inhibitor and a ligand for an E3 ubiquitin ligase via a linker to form a targeted protein degradation chimera. In vivo, the inhibitor portion of this bifunctional molecule recognizes the target protein, while the E3 ligase ligand portion recognizes the ubiquitin ligase, ultimately degrading the target protein through the ubiquitin-proteasome pathway. Protein degradation drugs can target “undruggable” targets, improve selectivity and inhibitory activity against targets, and prolong drug duration of action and resistance to mutations. They are particularly suitable for drug development against traditionally undruggable targets (such as transcription factors and scaffold proteins), targets prone to acquired resistance mutations during tumor targeted therapy, targets with gene amplification and / or protein overexpression, targets with different protein isoforms, scaffold proteins, protein aggregates, etc. Currently, small molecule inhibitors targeting EZH2 have been approved for marketing, clinically validating the feasibility of PRC2 as an anti-tumor drug target. However, the efficacy of EZH2 small molecule inhibitors remains limited in solid tumors, and multiple small molecule inhibitors of EZH2 and EED are still under clinical investigation. Considering the structural and functional characteristics of PRC2 and the advantages of protein degradation drugs, utilizing protein degradation technology for drug development against this target may bring new directions and breakthroughs to the drug development for this target. Although a protein degrader of EED has been reported in the literature (Cell Chemical Biology 2020, 27: 41-46.), its degradation activity and druggability still have significant room for improvement. Therefore, there remains a need to develop highly active EED degraders for clinical research. SUMMARY The purpose of the present application is to provide a PROTAC compound. The compound of the present application is able to degrade and / or inhibit EED proteins, exhibits an excellent degradation / inhibition effect on EED protein and an excellent inhibition effect on tumor cell proliferation, has excellent pharmacokinetic properties, low toxic side effects, good safety, and is more suitable for treating diseases or conditions associated with aberrant EED protein activity (such as proliferative diseases like cancer). A first aspect of the present application provides a compound of formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: POI—(L)n0—ULM (I), wherein POI is a ligand that binds to an EED protein; L is a linker linking POI and ULM; ULM is a group that binds to an E3 ligase; and n0 is 0 or 1. In some embodiments, n0 is 0. In some embodiments, n0 is 1. In some embodiments, POI is a structure of formula (A-1) or an isomer thereof: wherein, ring A1 is a 5- to 20-membered heterocycloalkyl ring (preferably a 5- to 6-membered heterocycloalkyl ring, preferably a 15- to 20-membered heterocycloalkyl ring, more preferably a 15- to 18-membered heterocycloalkyl ring, further preferably an 18-membered heterocycloalkyl ring) or a 5- to 10-membered heteroaryl ring (preferably an 8- to 10-membered heteroaryl ring, more preferably a 9-membered heteroaryl ring, more preferably a 10-membered heteroaryl ring); ring A2 is absent, or is a 3- to 15-membered heterocycloalkyl ring, a C3-10 cycloalkylring, a 5- to 15-membered heteroaryl ring (preferably a 5- to 12-membered heteroaryl ring, more preferably a 5- to 10-membered heteroaryl ring, further preferably a 5- to 6-membered heteroaryl ring) or a C6-10 aryl ring (preferably a benzene ring or a naphthalene ring); (R1)n1 represents substitution of hydrogen on 2,3-dihydrobenzofuran ring by n1 R1, n1 is 0, 1 or 2, each R1 is identical or different, and each R1 is independently selected from the group consisting of hydrogen, deuterium, halogen (preferably fluorine, chlorine or bromine), oxo, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy), -COC1-8 alkyl (preferably -COC1-6 alkyl, more preferably -COC1-3 alkyl), -OCOC1-8 alkyl (preferably -OCOC1-6 alkyl, more preferably -OCOC1-3 alkyl), -COOC1-8 alkyl (preferably -COOC1-6 alkyl, more preferably -COOC1-3 alkyl), -CONH2, -CONHC1-8 alkyl (preferably -CONHC1-6 alkyl, more preferably -CONHC1-3 alkyl), -CON(C1-8 alkyl)2 (preferably -CON(C1-6 alkyl)2, more preferably -CON(C1-3 alkyl)2), -SOC1-8 alkyl (preferably -SOC1-6 alkyl, more preferably -SOC1-3 alkyl), -SO2C1-8 alkyl (preferably -SO2C1-6 alkyl, more preferably -SO2C1-3 alkyl), -OSO2C1-8 alkyl (preferably -OSO2C1-6 alkyl, more preferably -OSO2C1-3 alkyl), -SO2NH2, -SO2NHC1-8 alkyl (preferably -SO2NHC1-6 alkyl, more preferably -SO2NHC1-3 alkyl), -SO2N(C1-8 alkyl)2 (preferably -SO2N(C1-6 alkyl)2, more preferably -SO2N(C1-3 alkyl)2), C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl); and / or two R1 and carbon atom linked to the two R1 together form a C3-15 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring) or a 3- to 15-membered heterocycloalkyl ring (preferably a 3- to 10-membered heterocycloalkyl ring, more preferably a 3- to 8-membered heterocycloalkyl ring, further preferably a 3- to 6-membered heterocycloalkyl ring); the C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, -COC1-8 alkyl, -COOC1-8 alkyl, -OCOC1-8 alkyl, -CONH2, -CONHC1-8 alkyl, -CON(C1-8 alkyl)2, -SOC1-8 alkyl, -SO2C1-8 alkyl, -OSO2C1-8 alkyl, -SO2NH2, -SO2NHC1-8 alkyl, -SO2N(C1-8 alkyl)2, C3-8 cycloalkyl, 3- to 12-membered heterocycloalkyl, 5- to 10-membered heteroaryl, C6-14 aryl, C3-15 cycloalkyl ring and 3- to 15-membered heterocycloalkyl ring are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: halogen, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl) and 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl); (R2)n2 represents substitution of hydrogen on ring A1 by n2 R2, n2 is 0, 1 or 2, each R2 is identical or different, and each R2 is independently selected from the group consisting of X1, hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy), -NHC1-8 alkyl (preferably -NHC1-6 alkyl, more preferably -NHC1-3 alkyl), -N(C1-8 alkyl)2 (preferably -N(C1-6 alkyl)2, more preferably -N(C1-3 alkyl)2), -COC1-8 alkyl (preferably -COC1-6 alkyl, more preferably -COC1-3 alkyl), -OCOC1-8 alkyl (preferably -OCOC1-6 alkyl, more preferably -OCOC1-3 alkyl), -COOC1-8 alkyl (preferably -COOC1-6 alkyl, more preferably -COOC1-3 alkyl), -CONH2, -CONHC1-8 alkyl (preferably -CONHC1-6 alkyl, more preferably -CONHC1-3 alkyl), -CON(C1-8 alkyl)2 (preferably -CON(C1-6 alkyl)2, more preferably -CON(C1-3 alkyl)2), -PO(C1-8 alkyl)2 (preferably -PO(C1-6 alkyl)2, more preferably -PO(C1-3 alkyl)2), -SOC1-8 alkyl (preferably -SOC1-6 alkyl, more preferably -SOC1-3 alkyl), -SO2C1-8 alkyl (preferably -SO2C1-6 alkyl, more preferably -SO2C1-3 alkyl), -OSO2C1-8 alkyl (preferably -OSO2C1-6 alkyl, more preferably -OSO2C1-3 alkyl), -SC1-6 alkyl, -SO2NH2, -SO2NHC1-8 alkyl (preferably -SO2NHC1-6 alkyl, more preferably -SO2NHC1-3 alkyl), -SO2N(C1-8 alkyl)2 (preferably -SO2N(C1-6 alkyl)2, more preferably -SO2N(C1-3 alkyl)2), C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl); the C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, -NHC1-8 alkyl, -N(C1-8 alkyl)2, -COC1-8 alkyl, -OCOC1-8 alkyl, -COOC1-8 alkyl, -CONH2, -CONHC1-8 alkyl, -CON(C1-8 alkyl)2, -PO(C1-8 alkyl)2, -SOC1-8 alkyl, -SO2C1-8 alkyl, -OSO2C1-8 alkyl, -SO2NH2, -SO2NHC1-8 alkyl, -SO2N(C1-8 alkyl)2, C3-8 cycloalkyl, 3- to 12-membered heterocycloalkyl, 5- to 10-membered heteroaryl, C6-14 aryl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: halogen, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -PO(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl); or R1, R2 and carbon atom linked to R1 and R2 together form a 6- to 15-membered heterocycloalkyl ring; the 6- to 15-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -PO(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl); (R3)n3 represents substitution of hydrogen on ring A2 by n3 R3, n3 is 0, 1, 2 or 3, each R3 is identical or different, and each R3 is independently selected from the group consisting of X1, hydrogen, deuterium, cyano, carboxyl, nitro, formyl, sulfo, halogen, oxo, C1-10 alkyl (preferably C1-8 alkyl, more preferably C1-6 alkyl, further preferably C1-3 alkyl), C1-10 haloalkyl (preferably C1-8 haloalkyl, more preferably C1-6 haloalkyl, further preferably C1-3 haloalkyl), C1-10 alkoxy (preferably C1-8 alkoxy, more preferably C1-6 alkoxy, further preferably C1-3 alkoxy), C1-10 haloalkoxy (preferably C1-8 haloalkoxy, more preferably C1-6 haloalkoxy, further preferably C1-3 haloalkoxy), -COC1-10 alkyl (preferably -COC1-8 alkyl, more preferably -COC1-6 alkyl, further preferably -COC1-3 alkyl), -OCOC1-10 alkyl (preferably -OCOC1-8 alkyl, more preferably -OCOC1-6 alkyl, further preferably -OCOC1-3 alkyl), -COOC1-10 alkyl (preferably -COOC1-8 alkyl, more preferably -COOC1-6 alkyl, further preferably -COOC1-3 alkyl), -CONH2, -CONHC1-10 alkyl (preferably -CONHC1-8 alkyl, more preferably -CONHC1-6 alkyl, further preferably -CONHC1-3 alkyl), -CON(C1-10 alkyl)2 (preferably -CON(C1-8 alkyl)2, more preferably -CON(C1-6 alkyl)2, further preferably -CON(C1-3 alkyl)2), -SOC1-10 alkyl (preferably -SOC1-8 alkyl, more preferably -SOC1-6 alkyl, further preferably -SOC1-3 alkyl), -SO2C1-10 alkyl (preferably -SO2C1-8 alkyl, more preferably -SO2C1-6 alkyl, further preferably -SO2C1-3 alkyl), -OSO2C1-10 alkyl (preferably -OSO2C1-8 alkyl, more preferably -OSO2C1-6 alkyl, further preferably -OSO2C1-3 alkyl), -SO2NH2, -SO2NHC1-10 alkyl (preferably -SO2NHC1-8 alkyl, more preferably -SO2NHC1-6 alkyl, further preferably -SO2NHC1-3 alkyl), -SO2N(C1-10 alkyl)2 (preferably -SO2N(C1-8 alkyl)2, more preferably -SO2N(C1-6 alkyl)2, further preferably -SO2N(C1-3 alkyl)2), C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 15-membered heterocycloalkyl (preferably 4- to 12-membered heterocycloalkyl, more preferably 4- to 8-membered heterocycloalkyl, further preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl; the C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, C1-10 haloalkoxy, -COC1-10 alkyl, -OCOC1-10 alkyl, -COOC1-10 alkyl, -CONH2, -CONHC1-10 alkyl, -CON(C1-10 alkyl)2, -SOC1-10 alkyl, -SO2C1-10 alkyl, -OSO2C1-10 alkyl, -SO2NH2, -SO2NHC1-10 alkyl, -SO2N(C1-10 alkyl)2, C3-8 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl, C6-14 aryl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-6 cycloalkyl, 3- to 15-membered heterocycloalkyl (preferably 4- to 12-membered heterocycloalkyl, more preferably 4- to 8-membered heterocycloalkyl, further preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl), phenyl and naphthyl; X1 in R2 and R3 is a point of attachment of POI to L or ULM, and at least one of R2 and R3 is X1. In some embodiments, ring A1 is an 8- to 10-membered heteroaryl ring. In some embodiments, ring A1 is a 9-membered heteroaryl ring or a 10-membered heteroaryl ring. In some embodiments, ring A1 is a 9-membered nitrogen-containing heteroaryl ring or a 10-membered nitrogen-containing heteroaryl ring. In some embodiments, ring A1 is selected from the group consisting of an indolizine ring, a pyrazolopyridine ring, an imidazopyridine ring, a triazolopyridine ring, a tetrazolopyridine ring, a pyrrolopyridazine ring, a pyrazolopyridazine ring, an imidazopyridazine ring, a triazolopyridazine ring, a tetrazolopyridazine ring, a pyrrolopyrimidine ring, a pyrazolopyrimidine ring, an imidazopyrimidine ring, a triazolopyrimidine ring, a tetrazolopyrimidine ring, a pyrrolopyrazine ring, a pyrazolopyrazine ring, an imidazopyrazine ring, a triazolopyrazine ring, a pyridopyridine ring, a pyridopyrazine ring, a pyridopyridazine ring, a pyridotriazine ring, a pyridopyrimidine ring and a tetrazolopyrazine ring. In some embodiments, ring A1 is selected from the group consisting of [1,2,4]triazolo[4,3-c]pyrimidine,         imidazo[1,5-c]pyrimidine,         imidazo[1,2-c]pyrimidine, [1,2,4]triazolo[4,3-a]pyridine and pyrido[3,4-d]pyridazine. In some embodiments, ring A1 is a 5- to 6-membered heterocycloalkyl ring. In some embodiments, ring A1 is selected from the group consisting of pyrimidin-4(3H)-one, 1,6-dihydropyrimidine, pyridin-2(1H)-one, 1,2-dihydropyridine and 3,8-diazabicyclo[3.2.1]octane. In some embodiments, ring A1 is an 18-membered heterocycloalkyl ring. In some embodiments, ring A1 is a partially unsaturated 18-membered heterocycloalkyl ring. In some embodiments, ring A1 is selected from the group consisting of 2,3-dihydro-7'H-spiro[indene-1,8'-pyrido[3,4-d]pyridazin]-7'-one                                and 2,3-dihydro-7'H-spiro[indene-1,8'-pyrido[4,3-c]pyridazin]-7'-one. In some embodiments, Xmx structures or isomers thereof: .            HnJ Xu    Xu ,   ,, N—N H T  ( )   lA CK.N^.NH    \__ /        V  ) Xj XX, X V         X  NX ,, A1 a —X   is selected from the group consisting of the following A.        xN        M         X          .N' G         f / / N      f 'N        f N        f N nx । x G x G x / G i x znXx > G hnX\ hnX\ H hnG / H hnX\ / H 1       —N          N-N ,,,  , a            GnTQ X                 N—''          N                N ,,    5   5 ,NX >              N" N H x P HrA a and       N-7   . In some embodiments, is selected from the group consisting of the following structures or isomers thereof: In some embodiments, structures or isomers thereof: group consisting of the following In some embodiments, is selected from the group consisting of the following structures or isomers thereof: and In some embodiments, POI is a structure of formula (A-2-1) or an isomer thereof: (A-2-1) 10 wherein, W1, W2, W3, W4, W5 and W6 are each independently CH or N; ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, POI is a structure of formula (A-2-2) or an isomer thereof: 15 wherein, W1, W2, W3, W4 and W5 are each independently CH or N; ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, POI is a structure of formula (A-3) or an isomer thereof: (A-3) wherein, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, POI is a structure of formula (A-4) or an isomer thereof: wherein, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, POI is a structure of formula (A-5) or an isomer thereof: 02(^2)^ N | HN—r A2 A (Rs)n3 (RJm N-7 (A-5) , wherein, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, POI is a structure of formula (A-6) or an isomer thereof: n2(R2k I HN—r A2 H (Rs)n3 (R^    N—7 (A-6) , wherein, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, POI is a structure of formula (A-7) or an isomer thereof: n2(R2)\ \_| z~\  A\ I-7  HN—--r A2 H (R3)n3 (R^    N—7 (A-7) , wherein, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, POI is a structure of formula (A-8) or an isomer thereof: (A-8) wherein, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in the specification, and at least one of R2 and R3 is X1. In some embodiments, ring A2 is absent or is selected from the group consisting of a 4- to 8-membered heterocycloalkyl ring, a C4-8 cycloalkyl ring, a 5- to 10-membered heteroaryl ring, a 10-to 15-membered heterocycloalkyl ring and a benzene ring. In some embodiments, ring A2 is absent or is selected from the group consisting of a 4- to 8-membered heterocycloalkyl ring, a saturated C4-8 cycloalkyl ring, a 5- to 10-membered heteroaryl ring, a partially unsaturated 10- to 15-membered heterocycloalkyl ring and a benzene ring. In some embodiments, ring A2 is absent or is selected from the group consisting of a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, an azetidine ring, a tetrahydropyrrole ring, a pyrazolidine ring, an imidazolidine ring, a piperidine ring, a hexahydropyridazine ring, a hexahydropyrimidine ring, a piperazine ring, a benzene ring, a pyrazole ring, an oxazole ring, an imidazole ring, a triazole ring, a tetrazole ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, an indolizine ring, pyrazolopyridine, imidazopyridine, triazolopyridine, tetrazolopyridine, pyrrolopyridazine, pyrazolopyridazine, imidazopyridazine, triazolopyridazine, tetrazolopyridazine, pyrrolopyrimidine, pyrazolopyrimidine, imidazopyrimidine, triazolopyrimidine, tetrazolopyrimidine, pyrrolopyrazine, pyrazolopyrazine, imidazopyrazine, triazolopyrazine, tetrazolopyrazine, pyridopyridine, pyridopyrazine, pyridopyridazine, pyridotriazine, pyridopyrimidine, 3,8-diazabicyclo[3.2.1]octane and 2,3-dihydrospiro[indene-1,4'-piperidine]. In some embodiments, ring A2 is absent or is selected from the group consisting of a saturated 6-membered heterocycloalkyl ring, a partially unsaturated 12-membered heterocycloalkyl ring, a cyclohexane ring, a 5- to 6-membered heteroaryl ring, a 9-membered heteroaryl ring and a benzene ring. In some embodiments, ring A2 is absent or is selected from the group consisting of a cyclohexane ring, a piperidine ring, a piperazine ring, a benzene ring, a pyridine ring, a pyrazole ring, a triazolopyridine ring and 2,3-dihydrospiro[indene-1,4'-piperidine]. In some embodiments, ring A2 is selected from the group consisting of a benzene ring, a pyridine ring and a pyrazole ring. In some embodiments, 1  ' A2) is selected from the group consisting of the following structures or isomers thereof: and In some embodiments, is selected from the group consisting of the following structures: and In some embodiments, In some embodiments, is selected from the group consisting of the following structures or isomers thereof: HZ} and Kn'h. In some embodiments, is selected from the group consisting of the following structures or isomers thereof: and In some embodiments, n1 is 0. In some embodiments, n1 is 1 or 2. In some embodiments, n1 is 1. In some embodiments, R1 is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, propoxy, isopropoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, pyrrolyl, pyrazolyl, pyridinyl, phenyl, pyrimidinyl, -CH2-cyclopropyl, -CH2-tetrahydropyrrolyl, -CH2-pyrrolyl, -CH2-phenyl, -CH2-pyridinyl, -CH2-cyclohexenyl, -CH2-azetidine, -CH2-piperidine, -CH2-piperazine, tetrahydro-2H-pyran and -CH2-(tetrahydro-2H-pyran). In some embodiments, R1 is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, iodine, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH2F, -CHF2, -CF3, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -OCH2F, -OCHF2, -OCF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -OCH2CH2F, -OCH2CHF2 and -OCH2CF3. In some embodiments, n1 is 1, and R1 is fluorine. In some embodiments, In some embodiments, In some embodiments, two R1 and carbon atom linked to the two R1 together form a cyclopropyl ring, a cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring, a cyclobutene ring, a cyclopentene ring, a cyclohexene ring, an azetidine ring, a tetrahydropyrrole ring, a piperidine ring or a piperazine ring. In some embodiments, two R1 and carbon atom linked to the two R1 together form a cyclopropyl ring. In some embodiments, n3 is 3, one R3 is fluorine, and the other two R3 and carbon atom linked to the other two R3 together form a cyclopropane ring. In some embodiments, In some embodiments, In some embodiments, R2 is selected from the group consisting of X1, hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -PO(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SC1-6 alkyl, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl and C1-6 haloalkoxy. In some embodiments, R2 is selected from the group consisting of X1, hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -COC1-3 alkyl, -COOC1-3 alkyl, -OCOC1-3 alkyl, -PO(C1-3 alkyl)2, -SOC1-3 alkyl, -SO2C1-3 alkyl, -OSO2C1-3 alkyl, -SC1-3 alkyl, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl and C1-3 haloalkoxy. In some embodiments, R2 is selected from the group consisting of X1, hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, -NHCH3, -N(CH3)2, -CONH2, -CONHCH3, -CON(CH3)2,  -COCH3, -COC(CH3)3,  -COOCH3, -COOCH2CH3, -COOC(CH3)3, -OCOCH3, -OCOCH2CH3, -OCOC(CH3)3, -PO(CH3)2, -PO(CH2CH3)2, -SOCH3, -SOCH2CH3, -SOC(CH3)3, -SO2CH3,  -SO2CH2CH3,  -SO2C(CH3)3, -OSO2CH3, -OSO2CH2CH3, -OSO2C(CH3)3,  -SCH3, -SCH2CH3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, monofluoropropyl, difluoropropyl, trifluoropropyl, monofluoroisopropyl, difluoroisopropyl, trifluoroisopropyl, monofluoro-tert-butyl, difluoro-tert-butyl, trifluoro-tert-butyl, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, monofluoropropoxy, difluoropropoxy, trifluoropropoxy, monofluoroisopropoxy, difluoroisopropoxy, trifluoroisopropoxy, monofluoro-tert-butoxy, difluoro-tert-butoxy and trifluoro-tert-butoxy. In some embodiments, R2 is selected from the group consisting of X1, hydrogen, halogen, cyano, -SO2C1-6 alkyl and -OSO2C1-6 alkyl. In some embodiments, R2 is selected from the group consisting of X1, hydrogen, halogen, cyano, -SO2C1-3 alkyl,and -OSO2C1-3 alkyl. In some embodiments, R2 is selected from the group consisting of X1, hydrogen, fluorine, chlorine, bromine, iodine, cyano, -SO2CH3 and -OSO2CH3. In some embodiments, R2 is selected from the group consisting of cyano, fluorine, chlorine, bromine, iodine, -CH3, -CF3, -SO2CH3, hydrogen and -PO(CH3)2. In some embodiments, R2 is selected from the group consisting of cyano, chlorine, bromine, -SO2CH3 and hydrogen. In some embodiments, n2 is 1, and R2 is selected from the group consisting of X1, hydrogen, fluorine, chlorine, bromine, iodine, -CH3, cyano, -SO2CH3, -OSO2CH3 and -PO(CH3)2. In some embodiments, n2 is 1, and R2 is selected from the group consisting of cyano, fluorine, chlorine, bromine, iodine, -CH3, -CF3, -SO2CH3, hydrogen and -PO(CH3)2. In some embodiments, n2 is 1, and R2 is selected from the group consisting of cyano, chlorine, bromine, -SO2CH3 and hydrogen. (R2)n2 In some embodiments,     XX X" n HnX\ structures or isomers thereof: f-N    X'X     A. ,NY 0      H nX X 11      SP-  xnY 1 ^X           0       N-X ,                                     , CN Xh x- Y" ”yX XX   HN—4 P—1 *      Nn<Y ,                                              , is selected from the group consisting of the following -N'm          A.,          X P i x nA । x nY       n zn a / M hnX Xh hnX\ Xxi x \\ Xx X         VJ' !       N-^       X       7 ,,,  , x            X           X NX\ , OMs    HN——1    HnXZ —1    HNYZ ] - 7' -7' cC ,,,  , 'nhXx0 / YYXi       I "T N~N I Pv           ( > X       / Y\_ /        ]  ||       / \ it ,N            Y / XX      I ( / N\ N           X                X ,  ,,, 10 COOC2H5 COOH and ; wherein X1 is the point of attachment to L or ULM. In some embodiments, , attachment to L or ULM. In some embodiments, is selected from the group consisting of the following structures or isomers thereof: , structures or isomers thereof: In some embodiments, ; wherein X1 is the point of is selected from the CN group consisting of the following is selected from the group consisting of the following structures or isomers thereof: and (R2)n2 In some embodiments, HN-P A1 is selected from the group consisting of the following structures or isomers thereof: and In some embodiments, R1, R2 and carbon atom linked to R1, R2 together form a 6- to 15-membered heterocycloalkyl ring, the 6- to 15-membered heterocycloalkyl ring is selected from the group consisting of 5,8-dihydro-4H-1,4-oxazocine, 4,5,8,9-tetrahydro-1,4-oxazepine, 5,8,9,10-tetrahydro-4H-1,4-oxazonine, and 1-oxa-4-azacycloundeca-2,6-diene; the 6- to 15-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of: fluorine, chlorine, bromine, iodine, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, methyl, ethyl, isopropyl, tert-butyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, isopropoxy, tert-butoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, -COCH3, -COCH2CH3, -COCH(CH3)2, -COC(CH3)3, -OCOCH3, -OCOCH2CH3, -OCOCH(CH3)2, -OCOC(CH3)3,  -CONH2, -CONHCH3, -CONHCH2CH3, -CONHCH(CH3)2, -CONHC(CH3)3, -CON(CH3)2, -CON(CH2CH3)2, -SOCH3, -SO2CH3, -SO2CH2CH3, -SO2CH(CH3)2, -SO2C(CH3)3, -OSO2CH3, -OSO2CH2CH3, -OSO2CH(CH3)2, -OSO2C(CH3)3, -SO2NH2, -SO2NHCH3, -SO2NHCH2CH3, -SO2NHCH(CH3)2, -SO2NHC(CH3)3, -SO2N(CH3)2, -SO2N(CH2CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, azetidinyl, tetrahydropyrrolyl, piperidinyl, piperazinyl, pyrrolyl, pyrazolyl, pyridinyl, phenyl and pyrimidinyl. In some embodiments, R1, R2 and carbon atom linked to R1, R2 together form 4,5,8,9-tetrahydro-1,4-oxazepine,                                    5,8-dihydro-4H-1,4-oxazocine, 5,8,9,10-tetrahydro-4H-1,4-oxazonine, or 1-oxa-4-azacycloundeca-2,6-diene. In some embodiments, R1, R2 and carbon  atom linked to R1, R2 together form (2Z,6Z)-4,5,8,9-tetrahydro-1,4-oxazepine,                   (2E,6Z)-4,5,8,9-tetrahydro-1,4-oxazepine, (2E,6E)-4,5,8,9-tetrahydro-1,4-oxazepine,                   (2Z,6E)-4,5,8,9-tetrahydro-1,4-oxazepine, (2Z,6Z)-5,8-dihydro-4H-1,4-oxazocine,                      (2E,6Z)-5,8-dihydro-4H-1,4-oxazocine, (2Z,6E)-5,8-dihydro-4H-1,4-oxazocine,                      (2E,6E)-5,8-dihydro-4H-1,4-oxazocine, (2Z,6Z)-5,8,9,10-tetrahydro-4H-1,4-oxazonine,        (2E,6Z)-5,8,9,10-tetrahydro-4H-1,4-oxazonine, (2Z,6E)-5,8,9,10-tetrahydro-4H-1,4-oxazonine,        (2E,6E)-5,8,9,10-tetrahydro-4H-1,4-oxazonine, (2Z,6Z)-1-oxa-4-azacycloundeca-2,6-diene,              (2E,6Z)-1-oxa-4-azacycloundeca-2,6-diene, (2Z,6E)-1-oxa-4-azacycloundeca-2,6-diene or (2E,6E)-1-oxa-4-azacycloundeca-2,6-diene. In some embodiments, R1, R2 and carbon  atom linked to R1, R2 together form (2Z,6Z)-4,5,8,9-tetrahydro-1,4-oxazepine,                    (2Z,6Z)-5,8-dihydro-4H-1,4-oxazocine, (2Z,6Z)-5,8,9,10-tetrahydro-4H-1,4-oxazonine or (2Z,6Z)-1-oxa-4-azacycloundeca-2,6-diene. O j In some embodiments, ( 4 H      I “0“(Rl)n1 z— / n2(R2> 3___ / 0              (R2)n2—( , '2(R2i\_ aXX. VAA / / \   \ H          ' , wherein — bond); n1 is 0 or 1, and n2 is 0 or 1. oz ] _J / A 5        In some embodiments, ( l)n1 L= (R2)n2 h          is selected from the group consisting of HN- x / ^               (R2)n2 H     / H "A1J\ Xi           i CAX / o ,         o-^               and — represents ------ (single bond) or ------ (double (R2)n2 YaXX^ h         is selected from the group consisting of (R )                                                 / R2)n2 N==> / (R2)n2                                    HN---^ / ==^ . /    3       H              II (Rl)n1                       {     N__ /         \\      \ nvA / AA>A           ft  LZ T Y \ / °        LX Ai . A. A     J— /               / == / o-\>6 V       0                                                 (Rl)n1 ,                                                                              , II A(R2)n2 A A-(Rl)n1 l / —n 1 A \ H       --- / o- ".Z           ;wherein n1 is 0 or 1, and n2 is 0 or 1. fRA . N v     1        H                   / / A N\^ N 'KaAAR' )m v^X\ / XX o- /               and In some embodiments "a h fYKi a h,n^ _A^„ Jk nvA Y Y l / ° LA .      JL       J— /           0' %         °-----'X. , 10       In some embodiments N^.    ='A^    l1^ HN--- M    '     H                  N    N-- / I T    \      \ A t k JI         ,\ /       ,W ^o'v A , In some embodiments, (aiYA (Rl)n1           HA 7                   J? _ .1 _ _ _ __ -X- _ ,        x— h          is selected from the group consisting of F\                     fZ2==2\ XS NXN H XX     L> Yl Xi vXX / -XX ^YY^nYAao ° ,        o-L       and      o—. (R2)n2 -Xa^A \ (aiYA (Ri)m \ / nA y ,                h          is selected from the group consisting of F\                                                   -N 3=¾ / N=i    fA^s\              faAA XX             la n\ kA "O vXX / ^° kAXX / 0 ,          o-^         and        o '■ /       . A\                          N==r\                ii °\J   <RY    nXn nKLY -Yv^ aLM  T Y   a / ° (Ri)m \ J nA Y ■ v^AAA___xz1—7 \=^    H          is =       0           . In some embodiments, R3 is selected from the group consisting of X1, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl; the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, halogen, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, -COC1-3 alkyl, -COOC1-3 alkyl, -CONH2, -CONHC1-3 alkyl, -CON(C1-3 alkyl)2, -SOC1-3 alkyl, -SO2C1-3 alkyl, -OSO2C1-3 alkyl, -SO2NH2, -SO2NHC1-3 alkyl, -SO2N(C1-3 alkyl)2, C3-6 cycloalkyl, 4- to 6-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl. In some embodiments, R3 is selected from the group consisting of X1, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl; the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, halogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy, -COCH3, -OCOCH3, -COOCH3,  -CONH2, -CONHCH3, -CON(CH3)2, -SOCH3,  -SO2CH3,  -SO2NH2, -SO2NHCH3, -SO2N(CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, azetidinyl, tetrahydropyrrolyl, piperidinyl, piperazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyrimidinyl, pyridazinyl and phenyl. In some embodiments, R3 is selected from the group consisting of X1, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CO2NH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl. In some embodiments, R3 is selected from the group consisting of X1, fluorine, chlorine, bromine, iodine, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, -COCH3, -COCH2CH3, -COC(CH3)3, -OCOCH3, -OCOCH2CH3, -OCOC(CH3)3, -COOCH3, -COOCH2CH3, -COOC(CH3)3, -CONH2, -CONHCH3, -CON(CH3)2, -SOCH3, -SO2CH3, -SO2C(CH3)3, -OSO2CH3, -OSO2C(CH3)3, -SO2NH2, -SO2NHCH3, -SO2N(CH3)2, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, azetidinyl, piperazinyl, piperidinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl and phenyl. In some embodiments, R3 is selected from the group consisting of X1, C1-6 alkyl, C3-8 cycloalkyl, C1-6 haloalkyl and -COC1-6 alkyl. In some embodiments, R3 is selected from the group consisting of X1, C1-3 alkyl, C3-6 cycloalkyl, C1-3 haloalkyl and -COC1-3 alkyl. In some embodiments, R3 is selected from the group consisting of X1, methyl, cyclopropyl, trifluoromethyl and -COCH3. In some embodiments, R3 is selected from the group consisting of X1, fluorine and methyl. In some embodiments, n3 is 0. In some embodiments, n3 is 1, and R3 is selected from the group consisting of X1, methyl, cyclopropyl, trifluoromethyl and -COCH3. In some embodiments, n3 is 1, and R3 is methyl. In some embodiments, n3 is 2, and R3 are X1 and methyl, respectively. (R3)n3 In some embodiments, is selected from the group consisting of the following structures or isomers thereof: point of attachment to L or ULM. and ; X1 is the (R3)n3 In some embodiments, is selected from the group consisting of the following structures or isomers thereof: of attachment to L or ULM. In some embodiments, (R3)n3 i AN I structures or isomers thereof:          Xl, \ N-N i / °'N rvA and        xi; X1 is the point selected from the group consisting of the following and ; X1 is the point of attachment to L or ULM. (R3)n3 In some embodiments, selected from the group consisting of the following i / ^N I VN. structures or isomers thereof:          Xl, X! I \ / / X1 and        n ; x1 is the point of attachment to L or ULM. (R3)n3 10 In some embodiments, selected from the group consisting of the following structures or isomers thereof: | \ / / xi and       N     ; x1 is the point of attachment to L or ULM. In some embodiments, POI is selected from the group consisting of the following structures or isomers thereof: and wherein X1 is the point of attachment to L or ULM. In some embodiments, POI is selected from the group consisting of the following structures or isomers thereof: and wherein X1 is the point of attachment to L or ULM. In some embodiments, POI is selected from the group consisting of the following structures or isomers thereof: and °' wherein X1 is the point of attachment to L or ULM. 5        In some embodiments, POI is selected from the group consisting of the following structures or isomers thereof: wherein X1 is the point of attachment to L or ULM. In some embodiments, POI is selected from the group consisting of the following structures or wherein X1 is the point of attachment to L or ULM. In some embodiments, L is a structure of formula (L-1) or an isomer thereof, -(La)m1- (L-1), wherein m1 is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each La at each occurrence is independently selected from the group consisting of a chemical bond, -C(O)-, -C(O)NRL1-, -NRL1-, -O-, -S-, C1-10 alkylene (preferably C1-8 alkylene, more preferably C1-6 alkylene, further preferably C1-3 alkylene), C1-10 alkyleneoxy (preferably C1-8 alkyleneoxy, more preferably C1-6 alkyleneoxy, further preferably C1-3 alkyleneoxy), C2-10 alkenylene (preferably C2-8 alkenylene, more preferably C2-6 alkenylene, further preferably C2-4 alkenylene), C2-10 alkynylene (preferably C2-8 alkynylene, more preferably C2-6 alkynylene, further preferably C2-4 alkynylene), a C3-15 cycloalkylene ring (preferably a C3-10 cycloalkylene ring, more preferably a C3-8 cycloalkylene ring, further preferably a C3-6 cycloalkylene ring), a 3- to 15-membered heterocycloalkylene ring (preferably a 4- to 12-membered heterocycloalkylene ring, more preferably a 4- to 10-membered heterocycloalkylene ring, further preferably a 4- to 8-membered heterocycloalkylene ring, further preferably a 4- to 6-membered heterocycloalkylene ring), a 5- to 15-membered heteroarylene ring (preferably a 5- to 14-membered heteroarylene ring, more preferably a 5- to 12-membered heteroarylene ring, further preferably a 5- to 10-membered heteroarylene ring, further preferably a 5-to 6-membered heteroarylene ring) and a C6-14 arylene ring (preferably a phenylene ring or a naphthylene ring); the C1-10 alkylene, C1-10 alkyleneoxy, C2-10 alkenylene, C2-10 alkynylene, C3-15 cycloalkylene ring, 3- to 15-membered heterocycloalkylene ring, 5- to 15-membered heteroarylene ring and C6-14 arylene ring are unsubstituted or substituted with 1, 2, 3 or 4 RL2, the each RL2 is independently selected from the group consisting of deuterium, halogen (preferably fluorine, chlorine or bromine), hydroxyl, cyano, amino, carboxyl, formyl, oxo, sulfo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy-substituted C1-6 alkyl, cyano-substituted C1-6 alkyl, amino-substituted C1-6 alkyl, C1-6 alkoxy C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl C1-6 alkyl, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl C1-6 alkyl, 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl C1-6 alkyl, phenyl, phenyl C1-6 alkyl, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl and -SO2N(C1-6 alkyl)2; each RL1 at each occurrence is independently selected from the group consisting of hydrogen, deuterium, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy) and C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl). In some embodiments, each RL1 at each occurrence is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, trifluoroethyl, difluoroethyl, monofluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, trifluoroethoxy, difluoroethoxy and monofluoroethoxy. In some embodiments, each RL1 at each occurrence is independently selected from the group consisting of hydrogen, methyl, ethyl, difluoromethyl and monofluoromethyl. In some embodiments, RL1 is hydrogen. In some embodiments, each RL2 is independently selected from the group consisting of deuterium, halogen (preferably fluorine, chlorine or bromine), hydroxyl, cyano, amino, carboxyl, hydroxymethyl, hydroxyethyl, methyl, ethyl, difluoromethyl, monofluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cyclopentenyl, tetrahydropyrrolyl, tetrahydrofuranyl, phenyl, pyrrolyl, furanyl, thienyl, thiazolyl, oxazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl,     -CH2-cyclopropyl,     -CH2-cyclobutyl,     -CH2-cyclopentyl,     -CH2-cyclohexyl, -CH2-cyclohexenyl,    -CH2-cyclopentenyl,    -CH2-tetrahydropyrrolyl,    -CH2-tetrahydrofuranyl, -CH2-phenyl, -CH2-pyrrolyl, -CH2-triazolyl, -CH2-tetrazolyl, -CH2-pyridinyl, -CH2-pyrazinyl, -CH2-triazinyl, methoxy, ethoxy, difluoromethoxy, monofluoromethoxy, trifluoromethoxy, acetyl, acetylamino and sulfonamido. In some embodiments, each RL2 is independently selected from the group consisting of deuterium, -F, -Cl, -Br, -OH, -CN, -CHO, -COOH, -NH2, -CH2OH, -CH2CH2OH, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -OCH3, -OCH2CH3, -OCH2F, -OCHF2, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -COCH3, -CH2-cyclopropyl, cyclopropyl, -CONH2, -COOCH3, -OCOCH3, -CONHCH3, -CON(CH3)2, -SOCH3, -SO2CH3, -SO2NH2, -SO2NHCH3 and -SO2N(CH3)2. In some embodiments, each RL2 is independently selected from the group consisting of deuterium, -F, -Cl, -Br, -OH, -CN, -COOH, -NH2, -CH2OH, -CH2CH2OH, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -OCH3, -OCH2CH3, -OCH2F, -OCHF2, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -COCH3, -CH2-cyclopropyl, cyclopropyl and -CONH2. In some embodiments, each RL2 is independently selected from the group consisting of fluorine, chlorine, bromine, hydroxy and hydroxymethyl. In some embodiments, each La is independently selected from the group consisting of the following structures or isomers thereof: -C(O)-, -C(O)NH-, -O-, -S-, -NH-, C1-10 alkylene, C1-10 alkyleneoxy, a C3-12 cycloalkylene ring, a 4- to 12-membered heterocycloalkylene ring, a 5- to 6-membered heteroarylene ring and a phenylene ring; the C3-12 cycloalkylene ring, 4- to 12-membered heterocycloalkylene ring, 5- to 6-membered heteroarylene ring and phenylene ring are unsubstituted or substituted with 1, 2, 3 or 4 RL2, and RL2 is selected from the group consisting of fluorine, hydroxy and hydroxymethyl. In some embodiments, each La is independently selected from the group consisting of the following structures or isomers thereof: -O-, -S-, -NH-, -C(O)-, -C(O)NH-, -(CH2)m2-, -O(CH2)m2-, -(CH2)m2O-, and a divalent form of a cyclic group selected from the group consisting of: a cyclopropane ring, a cyclobutane ring, a bicyclopentane ring, a cyclopentane ring, a cyclohexane ring, an azetidine ring, a tetrahydropyrrole ring, a piperidine ring, a piperazine ring, a hydroxy-substituted piperidine ring, a hydroxy-substituted piperazine ring, a hydroxymethyl-substituted piperidine ring, a hydroxymethyl-substituted piperazine ring, 3,3,5,5-tetramethylpiperidine, 3,3-difluoropiperidine, a 2-azaspiro[3.3]heptane ring, a 6-azaspiro[3.4]octane ring, a 7-azaspiro[3.5]nonane ring, a 2,6-diazaspiro[3.3]heptane ring, a 2,6-diazaspiro[3.4]octane ring, a 2,7-diazaspiro[3.5]nonane ring, a 2-azaspiro[3.5]nonane ring, a spiro[3.3]heptane ring, spiro[3.4]octane ring, a spiro[3.5]nonane ring, a 3,9-diazaspiro[5.5]undecane, a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, a triazine ring, a thiophene ring, a furan ring, a pyrrole ring, a thiazole ring, an oxazole ring, a pyrazole ring, an imidazole ring and a triazole ring; wherein each m2 at each occurrence is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, each La is independently selected from the group consisting of the following structures or isomers thereof: -(CH2)-, -(CH2)2-, -(CH2)5-, -C(O)-, -(CH2)3-, -C(O)NH-, / r i r a n vn                                 ROH —(CH?^-, -O-, -NH-,  ‘ v ,     '--- /  ’ ,      --- /    ,  *         * ,  '  \ /  ' , *  \= /   1 ,  '  \ /   ’ , In some embodiments, each La is independently selected from the group consisting of the following structures or isomers thereof: -(CH2)-, F L                   / X / X '—'    and ' vV i. In some embodiments, L is selected from the group consisting of the following structures or isomers thereof: -(CH2)m3-,  -C(O)-(CH2)m3-, -C(O)NH-(CH2)m3-, -C(O)NH-(CH2)m3-O-,  -Cy0-, -NH-Cy0-,     -Cy0-NH-(CH2)m3-,     -Cy0-(CH2)m3-NH-,     -Cy0-(CH2)m3-O-,     -C(O)NH-Cy0-, -(CH2)m3-C(O)NH-(CH2)m3-O-Cy0-O-(CH2)m3-,     -Cy0-Cy0-,     -(CH2)m3-Cy0-O-Cy0-O-(CH2)m3-, -Cy0-C(O)NH-Cy0-,  -Cy0-(CH2)m3-Cy0-,  -Cy0-O-Cy0-,  -Cy0-C(O)-Cy0-, -(CH2)m3-Cy0-Cy0 and -C(O)NH-(CH2)m3-Cy0-(CH2)m3-Cy0; wherein each m3 at each occurrence is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each Cy0 at each occurrence is independently selected from the group consisting of a C3-12 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring), a 3- to 12-membered heterocycloalkyl ring (preferably a 3- to 10-membered heterocycloalkyl ring, more preferably a 3- to 8-membered heterocycloalkyl ring, further preferably a 3- to 6-membered heterocycloalkyl ring), a 5- to 6-membered heteroaryl ring and a benzene ring; the C3-12 cycloalkyl ring, 3- to 12-membered heterocycloalkyl ring, 5- to 6-membered heteroaryl ring, benzene ring unsubstituted or substituted with 1, 2, 3 or 4 RL2, each RL2 at each occurrence is independently selected from the group consisting of deuterium, halogen, hydroxyl, cyano, amino, carboxyl, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, C1-3 haloalkoxy, C1-3 hydroxy alkyl, cyano-substituted C1-3 alkyl, amino-substituted C1-3 alkyl, C1-3 alkoxy C1-3 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl C1-3 alkyl, -COC1-3 alkyl, -COOC1-3 alkyl, -OCOC1-3 alkyl, -CONH2, -CONHC1-3 alkyl and -CON(C1-3 alkyl)2. In some embodiments, each Cy0 is independently selected from the group consisting of a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a bicyclopentane ring, a cyclohexane ring, an azetidine ring, a hydroxy-substituted azetidine ring, a tetrahydropyrrole ring, a piperidine ring, a hydroxy-substituted piperidine ring, a hydroxymethyl-substituted piperidine ring, a 4-fluoropiperidine ring, 3,3-difluoropiperidine, 3,3,5,5-tetramethylpiperidine, a piperazine ring, a 2-azaspiro[3.3]heptane ring, a 6-azaspiro[3.4]octane ring, a 7-azaspiro[3.5]nonane ring, a 2,6-diazaspiro[3.3]heptane ring, a 2,6-diazaspiro[3.4]octane ring, a 2,7-diazaspiro[3.5]nonane ring, a 2-azaspiro[3.5]nonane ring, a spiro[3.3]heptane ring, a spiro[3.4]octane ring, a spiro[3.5]nonane ring, 3,9-diazaspiro[5.5]undecane, a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, a triazine ring, a thiophene ring, a furan ring, a pyrrole ring, a thiazole ring, an oxazole ring, a pyrazole ring, an imidazole ring and a triazole ring. In some embodiments, each Cy0 is independently selected from the group consisting of a cyclobutane ring, a bicyclopentane ring, a benzene ring, an azetidine ring, a piperidine ring, a piperazine ring, and 3,9-diazaspiro[5.5]undecane. In some embodiments, each Cy0 is independently selected from the group consisting of a cyclobutane ring, an azetidine ring, a benzene ring, and a piperidine ring. In some embodiments, each Cy0 is independently selected from the group consisting of the following structures or isomers thereof: N Y N—I and   \—A— / . In some embodiments, each Cy0 is independently selected from the group consisting of the following structures or isomers thereof: In some embodiments, L is selected from the group consisting of the following structures or isomers thereof: ^oo^oo 10 and wherein X00 is a point of attachment of L to ULM or POI. In some embodiments, L is selected from the group consisting of the following structures or isomers thereof: and ; wherein X00 is the point of attachment of L to ULM or POI. In some embodiments, L is selected from the group consisting of the following structures or 15 00 isomers thereof: and wherein X00 is the point of attachment of L to ULM or POI. In some embodiments, L is selected from the group consisting of the following structures or isomers thereof: 10 15 wherein X00 is the point of attachment of L to ULM or POI. and In some embodiments, L is selected from the group consisting of the following structures or Xoo-N N-Xoo isomers thereof: POI. and °           ; wherein X00 is the point of attachment of L to ULM or In some embodiments, L is selected from the group consisting of the following structures or isomers thereof: *00 /  \    /   \ ' N / N N-Xoo and       f F         ; wherein X00 is the point of attachment of L to ULM or POI. In some embodiments, L is selected from the group consisting of the following structures or isomers thereof:  Xi°'— / x2o Xw X20 N"X20 H *10 ^10 /  \    /  \                                        V VN kN^N-X20     X10^^    __T-N' 20 f F         and        n            ; wherein x10 is a point of attachment of L to POI, and X20 is a point of attachment of L to ULM. In some embodiments, L is selected from the group consisting of the following structures or isomers thereof: and wherein X10 is the point of attachment of L to POI, and X20 is the point of attachment of L to ULM. In some embodiments, L is selected from the group consisting of the following structures or isomers thereof: Xio-Y'^ Y         K •„ V and o         ; wherein X10 is the point of attachment of L to POI, and X20 is the point of attachment of L to ULM. In some embodiments, L is selected from the group consisting of the following structures or 1 ff'^20     ^*20 x YJ       X10 N^x^ Xw^N'Y7 v -N Y 10'N^O           Y isomers thereof:       h        , xio          , H          and o           ; wherein X10 is the point of attachment of L to POI, and X20 is the point of attachment of L to ULM. In some embodiments, L is selected from the group consisting of the following structures or Xl0x^N^^^^X2Q        /  \             / \ .         x! r- H              X1O“N N-X20   X10-N >-X20 isomers thereof:    o          ,      \— /     ,       v     , 1O'N W H (r). \X2q           „ 7           7     / ^?>'X20 Xjo N''(s) H , / 0. , H 20 N '| N-X20 Xw^N 0 x2o and 20; wherein X10 is the point of attachment of L to POI, and X20 is the point of attachment of L to ULM. In some embodiments, L is selected from the group consisting of the following structures or •           .1 x- Xio-\ N-X20 isomers thereof:      \— and ; wherein X10 is the point of attachment of L to POI, and X20 is the point of attachment of L to ULM. In some embodiments, L is selected from the group consisting of the following structures or pN^20                   N^N^N-X20 isomers thereof:          N '         ,              n         and        F F          . wherein X10 is the point of attachment of L to POI, and X20 is the point of attachment of L to ULM. In some embodiments, ULM is a compound of formula (U-1) or an isomer thereof: X' "x            S-i S2 (RBi)bi—k- B 4—u0---S6 C ^3 --^S5—5¾ (RB2)b2 (U-l) wherein, ------represents         (double bond) or ------ (single bond); U0 is a chemical bond, -N(RU0)-, -CON(RU0)-, -CH2- or -(CH2)2-. each RU0 at each occurrence is independently hydrogen or C1-3 alkyl; ring B is absent or is selected from the group consisting of a 5- to 15-membered heteroaryl ring (preferably a 6- to 12-membered heteroaryl ring, more preferably a 6- to 10-membered heteroaryl ring), a 3- to 15-membered heterocycloalkyl ring (preferably a 5- to 12-membered heterocycloalkyl ring, more preferably a 5- to 10-membered heterocycloalkyl ring), a C3-15 cycloalkyl ring and a C6-10 aryl ring (preferably a benzene ring); S1, S3 and S5 are each independently selected from the group consisting of a chemical bond, -O-, -NH-, -N-, -CH2-, -CH-, -C(O)-, -C(O)O-, -C(O)S-, -CH2C(O)-, -CH2C(S)-, -C(S)-, -CONH-, -CH=N-, -N=N-, -CH=CH-, -SO- and -SO2-; S2 and S4 are each independently selected from the group consisting of -N-, -NH-, -CH- and -CH2-; S6 is selected from the group consisting of C, -CH- and N; (RB1)b1 represents substitution of hydrogen on ring B by b1 RB1, b1 is 0, 1, 2 or 3, each RB1 is identical or different, and each RB1 is independently selected from the group consisting of X2, deuterium, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl, hydroxyl, nitro, -NRa1Rb1, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), -SC1-8 alkyl (preferably -SC1-6 alkyl, more preferably -SC1-3 alkyl), -SOC1-8 alkyl (preferably -SOC1-6 alkyl, more preferably -SOC1-3 alkyl), -SO2C1-8 alkyl (preferably -SO2C1-6 alkyl, more preferably -SO2C1-3 alkyl), C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy), amino-substituted C1-8 alkyl (preferably amino-substituted C1-6 alkyl, more preferably amino-substituted C1-3 alkyl), cyano-substituted C1-8 alkyl (preferably cyano-substituted C1-6 alkyl, more preferably cyano-substituted C1-3 alkyl), hydroxy-substituted C1-8 alkyl (preferably hydroxy-substituted C1-6 alkyl, more preferably hydroxy-substituted C1-3 alkyl), carboxy-substituted C1-8 alkyl (preferably carboxy-substituted C1-6 alkyl, more preferably carboxy-substituted C1-3 alkyl), -COC1-8 alkyl (preferably -COC1-6 alkyl, more preferably -COC1-3 alkyl), -COOC1-8 alkyl-CONRa2Rb2 (preferably -COOC1-6 alkyl-CONRa2Rb2, more preferably -COOC1-3 alkyl-CONRa2Rb2), -SO2NRa2Rb2, a C3-15 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring), a 3- to 15-membered heterocycloalkyl ring (preferably a 4- to 12-membered heterocycloalkyl ring, more preferably a 4- to 10-membered heterocycloalkyl ring, 5 further preferably a 4- to 8-membered heterocycloalkyl ring, further preferably a 4- to 6-membered heterocycloalkyl ring), a 5- to 10-membered heteroaryl ring (preferably a 5- to 6-membered heteroaryl ring) and a C6-10 aryl ring (preferably a benzene ring or a naphthalene ring); or two adjacent RB1 and carbon atom linked to the two adjacent RB1 together form a C3-15 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring), a 310 to 15-membered heterocycloalkyl ring (preferably a 4- to 12-membered heterocycloalkyl ring, more preferably a 4- to 10-membered heterocycloalkyl ring, further preferably a 4- to 8-membered heterocycloalkyl ring, further preferably a 4- to 6-membered heterocycloalkyl ring), a 5- to 6-membered heteroaryl ring or a benzene ring; the C3-15 cycloalkyl ring, 3- to 15-membered heterocycloalkyl ring, 5- to 6-membered heteroaryl ring or benzene ring is unsubstituted or substituted 15 with 1, 2, 3 or 4 substituents selected from the group consisting of: X2, deuterium, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl, hydroxyl, nitro, -NRa1Rb1, C1-6 alkyl, C1-6 alkoxy, -SC1-6 alkyl, -SOC1-6 alkyl, -SO2C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, -COC1-6 alkyl, -COOC1-6 alkyl, -CONRa2Rb2 and -SO2NRa2Rb2; (RB2)b2 represents substitution of hydrogen on ring C by b2 RB2, b2 is 0, 1, 2, 3 or 4, each RB2 is 20 identical or different, and each RB2 is independently selected from the group consisting of X2, deuterium, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl, hydroxyl, -NRa1Rb1, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONRa2Rb2, -OC(O)C1-6 alkyl-substituted C1-6 alkyl and -COOC1-6 alkyl-substituted C1-6 alkyl; Ra1, Rb1, Ra2 and Rb2 are each independently selected from the group consisting of hydrogen, C1-6 25 alkyl, C1-6 haloalkyl, hydroxy-substituted C1-6 alkyl, cyano-substituted C1-6 alkyl, carboxy-substituted C1-6 alkyl, amino-substituted C1-6 alkyl, -COC1-6 alkyl and -COOC1-6 alkyl; X2 in RB1 and RB2 is a point of attachment of ULM to L or POI, and at least one of RB1 and RB2 is X2. In some embodiments, RB1 and RB2 are not both X2. 30        In some embodiments, ring B is absent. In some embodiments, the 5- to 15-membered heteroaryl ring in ring B is selected from the group consisting of a pyrrole ring, a furan ring, a thiophene ring, a pyrazole ring, an imidazole ring, a triazole ring, a tetrazole ring, an oxazole ring, a thiazole ring, an oxadiazole ring, a thiadiazole ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a triazine ring, a benzopyrrole ring, a 35 benzofuran ring, a benzothiophene ring, a benzopyrazole ring, a benzimidazole ring, a benzothiazole ring, a benzoxazole ring, a pyridopyrrole ring, a pyridofuran ring, a pyridothiophene ring, a pyridopyrazole ring, a pyridoimidazole ring, a pyridothiazole ring, a pyridooxazole ring, a pyrimidopyrrole ring, a pyridazopyrrole ring, a pyrazinopyrrole ring, a pyrimidopyrazole ring, a pyridazopyrazole ring, a pyrazinopyrazole ring, a pyrimidoimidazole ring, a pyridazoimidazole ring, a pyrazinoimidazole ring, a quinoline ring, an isoquinoline ring and a 9H-pyrido[2,3-b]indole ring. In some embodiments, the 5- to 15-membered heteroaryl ring in ring B is a benzopyrazole ring. In some embodiments, the 3- to 15-membered heterocycloalkyl ring in ring B is          Ss , wherein Q1, Q2, Q3 and Q4 are each independently selected from the group consisting of -CH-, N and N-O; S7 and S8 are each independently selected from the group consisting of a chemical bond, -O-, -NH-, -CH2-, -C(O)-, -C(O)O-, -C(O)S-, -CH2C(O)-, -CH2C(S)-, -C(S)-, -CONH-, -CH=N-, -N=N-, -CH=CH-, -SO- and -SO2-; represents a covalent connection to U0. In some embodiments, Q1, Q2, Q3 and Q4 are each independently -CH-. In some embodiments, S7 and S8 are each independently selected from the group consisting of -CH2- and -C(O)-. In some embodiments, S7 is -CH2- and S8 is -C(O)-. In some embodiments, S7 is -C(O)- and S8 is -C(O)-. | X $ 11 / N— In some embodiments, 'Qi     8      is selected from the group consisting of the following structures or isomers thereof:          0 and ; wherein represents a covalent connection to U0. In some embodiments, is selected from the group consisting of the following structures or isomers thereof: 0     and         0    ; wherein          represents a covalent connection to U0. In some embodiments, the 3- to 15-membered heterocycloalkyl ring in ring B is wherein ring B1 and ring B are each independently selected from the group consisting of a C4-8 cycloalkyl ring, a 4- to 8-membered heterocycloalkyl ring, a 5- to 6-membered heteroaryl ring and a benzene ring; S9 and S10 are each independently selected from the group consisting of a bond, -CH2- and -C(O)-; represents a covalent connection to U0. is selected from the group consisting of In some embodiments, connection to U0. and 0 ; wherein *sxsxsxs' represents a covalent In some embodiments, the 3- to 15-membered heterocycloalkyl ring in ring B is ; wherein ring B3 is a 3- to 7-membered heterocycloalkyl, represents a covalent connection to U0. In some embodiments, ring B3 is a 5- to 7-membered nitrogen-containing heterocycloalkyl ring. In some embodiments, ring B3 is a partially unsaturated 5- to 7-membered nitrogen-containing heterocycloalkyl ring. In some embodiments, ring B3 is selected from the group consisting of 2,5-dihydro-1H-pyrrole, 2,3-dihydro-1H-pyrrole,            1,2,3,6-tetrahydropyridine,            1,2,3,4-tetrahydropyridine, 2,3,6,7-tetrahydro-1H-azepine, 2,3,4,7-tetrahydro-1H-azepine and 2,3,4,5-tetrahydro-1H-azepine. In some embodiments, is selected from the group consisting of 0              0                o and 0 ; wherein          represents a covalent connection to U0. In some embodiments, is o o ; wherein 'jxsxsxs' represents a covalent connection to U0. In some embodiments, ring B is selected from the group consisting of: a benzene ring, HN-N ; wherein v / x / x / x / ' represents a covalent connection to U0. In some embodiments, ring B is selected from the group consisting of: a benzene ring, to U0. HN-N / \\ . and          ; wherein - / x / xz-v-' represents a covalent connection o In some embodiments, ring B is selected from the group consisting of:      o , f / p HN— / and           ; wherein v / x / x / xr* represents a covalent connection to U0. In some embodiments, each RB1 is independently X2, deuterium, fluorine, chlorine, bromine, cyano, carboxyl, hydroxyl, nitro, -NH2, -N(CH3)2, -NHCH3, -NHCOCH3, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, -SCH3, -SOCH3, -SO2CH3, -CH2NH2, -(CH2)2NH2, -(CH2)3NH2, -CH2CN, -(CH2)2CN, -(CH2)3CN, -CH2OH, -(CH2)2OH, -(CH2)3OH, -CH2COOH, -(CH2)2COOH, -(CH2)3COOH, -COCH3, -COCH2CH3, -COOCH3, -COOCH2CH3, -CONH2 or -SO2NH2; or two adjacent RB1 and carbon atom linked to the two adjacent RB1 together form a cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring, a cycloheptyl ring, a cyclopentene ring, a cyclohexene ring, a cycloheptene ring, a tetrahydropyrrole ring, a tetrahydrofuran ring, a tetrahydrothiophene ring, a piperidine ring, a pyrazine ring, a 1,2,3,4-tetrahydropyridine ring, a 1,2,3,4-tetrahydropyran ring, a 3,4-dihydro-2H-1,4-oxazine ring, a 2,3,4,5-tetrahydro-1H-azepine ring, a pyrrole ring, a pyrazole ring, an oxazole ring, a thiazole ring, a pyran ring, a pyridine ring, a pyridazine ring, a pyrimidine ring or a benzene ring; wherein the cyclobutyl ring, cyclopentyl ring, cyclohexyl ring, cycloheptyl ring, cyclopentene ring, cyclohexene ring, cycloheptene ring, tetrahydropyrrole ring, tetrahydrofuran ring, tetrahydrothiophene ring, piperidine ring, pyrazine ring, 1,2,3,4-tetrahydropyridine ring, 1,2,3,4-tetrahydropyran ring, 3,4-dihydro-2H-1,4-oxazine ring, 2,3,4,5-tetrahydro-1H-azepine ring, pyrrole ring, pyrazole ring, oxazole ring, thiazole ring, pyran ring, pyridine ring, pyridazine ring, pyrimidine ring or benzene ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of: X2, deuterium, fluorine, chlorine, bromine, cyano, carboxyl, hydroxyl, nitro, amino, methyl, trifluoromethyl, methoxy, trifluoromethoxy, -SCH3, -SOCH3, -SO2CH3, -COCH3, -COOCH3, -CONH2 and -SO2NH2. In some embodiments, RB1 is selected from the group consisting of X2, fluorine, chlorine, hydroxyl, methyl, trifluoromethyl and methoxy. In some embodiments, b1 is 1, and RB1 is fluorine. In some embodiments, b1 is 1, and RB1 is methyl. (RBl)bl--C— B -J-- In some embodiments,                       is selected from the group consisting of: and wherein X2 is the point of attachment of ULM to L or POI,         represents a covalent connection to U0. In some embodiments, is selected from the group consisting of: \ n-n wherein X2 is the point of attachment of ULM to L or POI,         represents a covalent connection to U0. (RBl)bf--£- B -J--1 In some embodiments,                      is selected from the group consisting of: O                \ o and x2 ^     , wherein X2 is the point of attachment of ULM to L or POI, represents a covalent connection to U0. In some embodiments, U0 is a chemical bond. In some embodiments, U0 is -NH-. In some embodiments, U0 is -CONH-. In some embodiments, U0 is -CH2-. In some embodiments, S1 and S3 are -C(O)-, S2 is -NH-, and S4 and S5 are -CH2-. In some embodiments, S6 is -CH-. In some embodiments, S6 is N. In some embodiments, b2 is 0. / Si —s2 —S6 ^.Ss In some embodiments,      $5 S4 ' B2tb2 is selected from the group consisting of the following structure or an isomer thereof: (RB2)b2  ; wherein          represents a covalent connection to U0. Si S2 —S6 ^§3 In some embodiments,      $5 S4 t B2)b2 is selected from the group consisting of the following °w                 0    / Anh     W r\ T° FT )=° structures or isomers thereof:    '—'     and    \— / ; wherein          represents a covalent connection to U0. In some embodiments, ULM is selected from the group consisting of the following structures or 10 isomers thereof: N-N 9>                        u O A. A-Z' N H             N -Ah TiXa XT Ta X> N          and x2           0; wherein X2 is the point of attachment of ULM to L or POI. 15 In some embodiments, ULM is selected from the group consisting of the following structures or isomers thereof: o and ; wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, ULM is selected from the group consisting of the following structure or an isomer thereof: ; wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, ULM is selected from the group consisting of the following structures or isomers thereof: x2 o and x ; wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, ULM is a structure of formula (U-2) or an isomer thereof: (U-2), wherein, r1 is 0, 1 or 2; ring D is selected from the group consisting of a benzene ring, a 5- to 6-membered heteroaryl ring, a C3-10 cycloalkyl ring (preferably a C3-8 cycloalkyl ring, more preferably a C3-6 cycloalkyl ring) and a 3- to 10-membered heterocycloalkyl ring (preferably a 3- to 8-membered heterocycloalkyl ring, more preferably a 3- to 6-membered heterocycloalkyl ring); (RU2)r2 represents substitution of hydrogen on ring D by r2 RU2, r2 is 0, 1, 2 or 3, each RU2 is identical or different, and each RU2 is independently selected from the group consisting of X2, hydrogen, deuterium, halogen (preferably fluorine, chlorine), nitro, cyano, carboxyl, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy C1-6 alkyl, hydroxy-substituted C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkyl, -NRa3Rb3, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -SC1-6 alkyl, 5- to 6-membered heteroaryl and phenyl; the 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, C1-6 alkyl (preferably C1-3 alkyl), hydroxy-substituted C1-6 alkyl (preferably hydroxy-substituted C1-3 alkyl), C1-6 alkoxy C1-6 alkyl (preferably C1-3 alkoxy C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (preferably C1-3 haloalkoxy), -NH2, -NHCOC1-6 alkyl (preferably -NHCOC1-3 alkyl), -COC1-6 alkyl (preferably -COC1-3 alkyl), -COOC1-6 alkyl (preferably -COOC1-3 alkyl), -OCOC1-6 alkyl (preferably -OCOC1-3 alkyl), -CONH2, -NHCONH2, -CONHC1-6 alkyl (preferably -CONHC1-3 alkyl), -NHCONHC1-6 alkyl (preferably -NHCONHC1-3 alkyl), -SOC1-6 alkyl (preferably -SOC1-3 alkyl), -SO2C1-6 alkyl (preferably -SO2C1-3 alkyl) and -SC1-6 alkyl (preferably -SC1-3 alkyl); RU1 is -C(RU3RU4)-U1; U1 is selected from the group consisting of the following structures or isomers thereof: X2, XA Ru" if /                       ilm -NHCO-X2, -NHCOCH3,       0     , a 5- to 6-membered heteroaryl ring,             and O5h            O^N^ O3h N        , the 5- to 6-membered heteroaryl ring,              and N         are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: X2, halogen, hydroxyl, cyano, amino, carboxyl, C1-6 alkyl (preferably methyl, ethyl, isopropyl), C1-6 alkoxy (preferably methoxy, ethoxy, isopropoxy), C1-6 haloalkyl (preferably trifluoromethyl), C1-6 haloalkoxy (preferably trifluoromethoxy), -COC1-6 alkyl (preferably -COCH3), -COOC1-6 alkyl (preferably -COOCH3), -CONH2, -CONHC1-6 alkyl (preferably -CONHCH3), -CON(C1-6 alkyl)2 (preferably -CON(CH3)2) and hydroxy-substituted C1-6 alkyl (preferably -CH2OH); RUa is selected from the group consisting of hydrogen, halogen (preferably fluorine, chlorine or bromine), cyano, hydroxyl, carboxyl, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -COC1-6 alkyl, -NHCOC1-6 alkyl, -N(C1-6 alkyl)COC1-6 alkyl, -NHC1-6 alkyl and -N(C1-6 alkyl)2; RU3 and RU4 are each independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), C1-6 haloalkyl (preferably C1-3 alkoxy), C1-6 haloalkoxy (preferably C1-3 haloalkoxy) and -SC1-6 alkyl (preferably -SC1-3 alkyl); or RU3, RU4 and carbon atom linked to RU3 and RU4 together form a C3-7 cycloalkyl (preferably C3-6 cycloalkyl) and a 3- to 7-membered heterocycloalkyl (preferably a 4-to 6-membered heterocycloalkyl); wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -SC1-6 alkyl, C3-7 cycloalkyl and 3- to 7-membered heterocycloalkyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: X2, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl and hydroxy; RU5 and RU6 are each independently selected from the group consisting of X2, hydrogen, deuterium, halogen, amino, cyano, carboxyl, hydroxyl, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (C1-3 haloalkoxy), -SC1-6 alkyl (preferably -SC1-3 alkyl), CONHC1-6 alkyl-substituted C1-6 alkyl, CON(C1-6 alkyl)2-substituted C1-6 alkyl, carboxyl-substituted C1-6 alkyl and COOC1-6 alkyl-substituted C1-6 alkyl; RU7 is selected from the group consisting of hydrogen, C1-6 alkyl, and C1-6 haloalkyl; or RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a 3- to 8-membered heterocycloalkyl ring or a 5- to 6-membered heteroaryl ring; RU8 is selected from the group consisting of hydroxyl, amino, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C1-6 alkoxy, C1-6 haloalkoxy and -OCOC1-6 alkyl; Ra3 and Rb3 are each independently selected from the group consisting of hydrogen, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), -SC1-6 alkyl (preferably -SC1-3 alkyl), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (preferably C1-3 haloalkoxy), -COC1-6 alkyl (preferably -COC1-3 alkyl), -CONH2, -CONHC1-6 alkyl (preferably -CONHC1-3 alkyl), -CON(C1-6 alkyl)2 (preferably -CON(C1-3 alkyl)2), 5- to 6-membered heteroaryl and phenyl; wherein the 5- to 6-membered heteroaryl and phenyl are each independently unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: hydrogen, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), -SC1-6 alkyl (preferably -SC1-3 alkyl), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (preferably C1-3 haloalkoxy), -COC1-6 alkyl (preferably -COC1-3 alkyl), -CONH2, -CONHC1-6 alkyl (preferably -CONHC1-3 alkyl) and -CON(C1-6 alkyl)2 (preferably -CON(C1-3 alkyl)2); X2 in RU2, RU1, RU5 and RU6 is the point of attachment of ULM to L or POI, and at least one of RU1, RU5, RU6 and RU2 is X2. In some embodiments, r1 is 0. In some embodiments, r1 is 1. In some embodiments, r1 is 2. In some embodiments, ring D is selected from the group consisting of a benzene ring, a 5- to 6-membered heteroaryl ring, a C5-9 cycloalkyl ring and a 5- to 9-membered heterocycloalkyl ring. In some embodiments, ring D is selected from the group consisting of a benzene ring and 2,3-dihydro-1H-indene. In some embodiments, ring D is a benzene ring. In some embodiments, ring D is 2,3-dihydro-1H-indene. In some embodiments, ring D is selected from the group consisting of a benzene ring and a 5- to 6-membered heteroaryl ring. In some embodiments, ring D is selected from the group consisting of a benzene ring, a pyrrole ring, a thiophene ring, a furan ring, a pyrazole ring, an imidazole ring, a triazole ring, a thiazole ring, an oxazole ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a piperidine ring, a piperazine ring and a tetrahydropyrrole ring. In some embodiments, ring D is selected from the group consisting of a benzene ring and a pyridine ring. In some embodiments, r1 is 0, and ring D is 2,3-dihydro-1H-indene. In some embodiments, r1 is 1, and ring D is a benzene ring. In some embodiments, r2 is 0. In some embodiments, r2 is 1. In some embodiments, r2 is 2. In some embodiments, RU2 is 5- to 6-membered heteroaryl or phenyl, the 5- to 6-membered heteroaryl or phenyl is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: deuterium, halogen (preferably fluorine, chlorine), cyano, carboxyl, hydroxyl, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, C1-3 haloalkoxy, -NH2, -NHCOC1-3 alkyl, -COC1-3 alkyl, -COOC1-3 alkyl, -OCOC1-3 alkyl, -CONH2, -NHCONH2, -CONHC1-3 alkyl, -NHCONHC1-3 alkyl, -SOC1-3 alkyl, -SO2C1-3 alkyl and -SC1-3 alkyl. In some embodiments, the 5- to 6-membered heteroaryl is selected from the group consisting of thiazolyl, oxazolyl, pyrazolyl, imidazolyl, pyrrolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, tetrazolyl and triazolyl. In some embodiments, the 5- to 6-membered heteroaryl is selected from the group consisting of In some embodiments, the 5- to 6-membered heteroaryl is and In some embodiments, the 5- to 6-membered heteroaryl ring is selected from the group consisting of a thiazole ring, an oxazole ring, a pyrazole ring, an imidazole ring, a pyrrole ring, a pyridine ring, a pyrimidine ring, a pyridazine ring, a pyrazine ring, a tetrazole ring and a triazole ring. In some embodiments, RU2 is cyano. In some embodiments, Ra3 and Rb3 are each independently selected from the group consisting of hydrogen, 5- to 6-membered heteroaryl and phenyl; the 5- to 6-membered heteroaryl is selected from the group consisting of thiazolyl, oxazolyl, pyrazolyl, imidazolyl, thienyl, furyl, pyrrolyl, triazolyl and tetrazolyl; the 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of: hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, trifluoromethoxy, -COCH3 and -CONH2. In some embodiments, RU2 is -NHRa3, wherein Ra3 is 5- to 6-membered heteroaryl or phenyl, and the 5- to 6-membered heteroaryl is selected from the group consisting of thiazolyl, imidazolyl, pyrazolyl, oxazolyl, pyridinyl and pyrimidinyl; wherein the 5- to 6-membered heteroaryl or phenyl is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: C1-3 alkoxy, C1-3 haloalkoxy, C1-3 alkyl, C1-3 haloalkyl, -SC1-3 alkyl and -OCOC1-3 alkyl. In some embodiments, RU2 is -NHRa3, wherein Ra3 is thiazolyl; and the thiazolyl is substituted with 1, 2 or 3 substituents selected from the group consisting of: methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy and trifluoroethoxy. In some embodiments, RU2 is -NHRa3, wherein Ra3 is thiazolyl; and the thiazolyl is substituted with 1, 2 or 3 substituents selected from the group consisting of: methyl, ethyl, propyl and isopropyl. In some embodiments, RU2 is selected from the group consisting of following structure: cyano, £ "4 1 and In some embodiments, r2 is 1, and RU2 is selected from the group consisting of cyano, N—| i and In some embodiments, r2 is 1, and RU2 is 10 In some embodiments, r2 is 2, and RU2 are X2 and , respectively. of ULM to L or POI. (RU2)r2 In some embodiments, is selected from the group consisting of the following structure or an isomer thereof: 15 In some embodiments, one of RU1, RU5, RU6 and RU2 is X2. In some embodiments, RUa is selected from the group consisting of fluorine, cyano, methyl, ethyl, trifluoromethyl and trifluoromethoxy. In some embodiments, RUa is selected from the group consisting of fluorine and cyano. In some embodiments, U1 is selected from the group consisting of X2, -NHCO-X2, -NHCOCH3, and ; wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, U1 is selected from the group consisting of -NHCO-X2 and wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, RU3 and RU4 are each independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy or C1-6 haloalkoxy; or RU3, RU4 and carbon atom linked to RU3 and RU4 form a C3-6 cycloalkyl ring. In some embodiments, RU3 and RU4 are each independently hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CF3, -CHF2, -CH2F, -OCH3, -OCH(CH3)2, -OC(CH3)3, -OCF3, -OCHF2, -OCH2F, fluoro-substituted isopropyl or fluoro-substituted tert-butyl; or RU3, RU4 and carbon atom linked to RU3 and RU4 form a cyclopropyl ring, a cyclobutyl ring, a cyclopentyl ring or a cyclohexyl ring. In some embodiments, RU3 and RU4 are each independently hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2 or -C(CH3)3; or RU3, RU4 and carbon atom linked to RU3 and RU4 form a cyclopropyl ring. In some embodiments, RU3 and RU4 are each independently hydrogen, -CH(CH3)2 or -C(CH3)3. In some embodiments, RU1 is selected from the group consisting of the following structures or isomers thereof: , or POI. ; wherein X2 is the point of attachment of ULM to L In some embodiments, RU1 is selected from the group consisting of the following structures: ; wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, RU1 is selected from the group consisting of the following structure: ; wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, RU5 and RU6 are each independently X2, hydrogen, deuterium, halogen, hydroxyl, carboxyl, cyano, amino, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl or C1-3 haloalkoxy; or RU5 and carbon atom on ring D together form a C3-6 cycloalkyl ring; wherein the C3-6 cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of: deuterium, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl, hydroxyl, nitro, formyl, sulfo, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C1-6 alkyl, C1-6 alkoxy, -SC1-6 alkyl, -SOC1-6 alkyl, -SO2C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, amino-substituted C1-6 alkyl, cyano-substituted C1-6 alkyl, hydroxy-substituted C1-6 alkyl, carboxyl-substituted C1-6 alkyl, -COC1-6 alkyl, -CO2NH2, -CO2NH(C1-6 alkyl), -CO2N(C1-6 alkyl)2, -SO2NH2, -SO2NH(C1-6 alkyl), -SO2N(C1-6 alkyl)2, a C3-8 cycloalkyl ring, a 4- to 10-membered heterocycloalkyl ring, a 5- to 6-membered heteroaryl ring and a benzene ring. In some embodiments, RU5 and RU6 are each independently hydrogen, C1-3 alkyl or C1-3 haloalkyl. In some embodiments, RU5 and RU6 are each independently hydrogen, -CH3, -OCH3, -CF3, -OCF3, -CHF2, -CH2F, -OCHF2 or -OCH2F. In some embodiments, RU5 and RU6 are each independently hydrogen or -CH3. In some embodiments, RU7 is selected from the group consisting of hydrogen, methyl, ethyl, monofluoromethyl, difluoromethyl and trifluoromethyl. In some embodiments, RU7 is hydrogen. In some embodiments, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a partially unsaturated 3- to 8-membered heterocycloalkyl ring, a 5- to 6-membered heteroaryl ring or a benzene ring. In some embodiments, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a tetrahydropyrrole ring, a pyrazolidine ring, an imidazolidine ring, a piperazine ring, a piperidine ring, a 2,3-dihydro-1H-pyrrole ring, a 2,3-dihydro-1H-pyrazole ring, a pyrrole ring, a pyrazole ring, an imidazole ring, a pyridine ring, a pyrimidine ring or a benzene ring. In some embodiments, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a 4- to 6-membered heterocycloalkyl ring. In some embodiments, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a 5-membered heterocycloalkyl ring. In some embodiments, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a tetrahydropyrrole ring. In some embodiments, is selected from the group consisting of the following structures or isomers thereof: ; wherein X2 is the point of attachment of In some embodiments, is selected from the group consisting of the following structures or isomers thereof: and 10 In some embodiments, RU8 is selected from the group consisting of hydroxyl, amino, -NH(C1-3 alkyl), -N(C1-3 alkyl)2, C1-3 alkoxy, fluoro C1-3 alkoxy and -OCOC1-3 alkyl. In some embodiments, RU8 is selected from the group consisting of hydroxyl, amino, -NH(CH3), 15 -N(CH3)2, -OCH3, -OCF3 and -OCOCH3. In some embodiments, RU8 is hydroxyl. In some embodiments, ULM is selected from the group consisting of the following structures or isomers thereof: and wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, ULM is selected from the group consisting of the following structures or isomers thereof: HO wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, ULM is selected from the group consisting of the following structures or isomers   thereof: wherein X2 is the point of attachment of ULM to L or POI. In some embodiments, the compound of formula (I) is a structure of formula (I-A), 10 (l-A) wherein, ring A1, ring A2, R1, n1, R2, n2, R3, n3, L, n0 and ULM are as defined in the specification, and both R2 and R3 are not X1. In some embodiments, the compound of formula (I) is a structure of formula (I-B), 15 wherein, ring A1, ring A2, R1, n1, R2, n2, R3, n3, L, n0 and ULM are as defined in the specification, and both R2 and R3 are not X1. In some embodiments, the compound of formula (I) is selected from the group consisting of the following structures or isomers thereof: wherein, ring A2, R1, n1, R2, n2, R3, n3, L, n0 and ULM are as defined in the specification, and both R2 and R3 are not X1. In some embodiments, the compound of formula (I) is selected from the group consisting of the following structures or isomers thereof: (L)n0-ULM (L)n0-ULM (LWULM (L)no-ULM (L)n0-ULM y-(L)n0-ULM (L)no-ULM (L)no-ULM (L)n0-ULM and ; wherein, L, n0 and ULM are as defined in the specification. In some embodiments, the compound of formula (I) is selected from the group consisting of the following structures or isomers thereof: (L)no-ULM and (LUULM wherein, L, n0 and ULM are as defined in the specification. 5        In some embodiments, the compound of formula (I) is selected from the group consisting of the following structures or isomers thereof: and wherein, L, n0 and ULM are as defined in the specification. In some embodiments, the compound of formula (I) is selected from the group consisting of the following structures or isomers thereof: and wherein, L, n0, and ULM are as defined in the specification. In some embodiments, the compound of formula (I) is a specific compound selected from the Examples. In some embodiments, the compound of formula (I) is a compound selected from Table A or a stereoisomer thereof: Table A In some embodiments, the compound of formula (I) is a compound selected from Table B or a stereoisomer thereof: Table B H131 H133 H135 N H137 H138 H139 H141 H143 H145 H147 H149 H150 H152 H154 H156 H160 H162 H164 H165 / \                          \    0 o 1                                        n-n \\ fY JVC'    nt>o \= / HN—\ / Mn,x\ / x KO f H T ’ I ? N. N       A / V H172 A       vvH° bbl MM ,       / = / F    ' V z,NM       z~~n nMM V ,—z \ i x N ''a         / ^ / H173 oQ        M" KM tm"1 ,, mm VVV M M» UJJ H174 0 r>^\                      x N Mh ? \                       N'y / V=o Ax A7 ' n-^                A=A F HN~Y     N           z—N n-AA aaa vA 4 jl Az \ n-A^ N^CI        7 H175 v         C'V Y L   xA^0 I A   M , v / -mm NMMN I I MU M m NM N      F H176 O-M                                  0 i \                                            H H A-A                   F- MM / N   N H A      , A Aa0 F hnMS        bj b X     / xN'b nMM^n \ 1 <\ ¥ X mX-M nMi N       F H177 A            xnX y™ n M                   U. ZN \ X° MM N>       M F HN^ Y jACA^ A n'N     MN'^^ H178 D       bAb° bbiN M'S          Jm F \ Lmn      Z^n 4a^aAaa Ca H179 / M z-b zyL '    / z z=< J s A 00 \=z b o A          "n'nAa ^a^An aa m           5^= / F A LA     / ^n NA^\ Aa—\ t ) VN H181 OZ                            °x M /               xn'\ XM ml       AA° Am    G> F A / m m < " W L y N'N      MN'b^ / H182 °M                         °s A       lata Aa   a "AA A n"n      MN'b^ / H183 oA                                 °\\ F HNM 1         Y nMM  M n, o UM ' k / N"N H184 O^b           .                \-N U \—(             \                     / \\ Anh #b—,        / N~n           ZaZ \ Cz, An-u rvY / - X J F / NM T । I ? । unmCi Vbb F H185 0 0A                   x N Anh V HN-M b \ F \ LAn     an V ny \ b mm \ ) F 4 Jl       n-m^ N^CI H186 A        vnA>° ^'CCnM'S           Jm H    \ U__MN        z^N \ N -M    V / b \ J F Um Z'm. nm^ / N^CI     ^m H187 o L ^Z / co 00 o ZK / \ Azmz ^z Am" °M                        °w M          "n'VTL f 1             M / \M M Nx       fl F HY Yn  mA 4jX / Lm jv f N't,     b_ / N H189 H190 H192 H194 o H196 H198 H200 H202 H204 H206 H208 H209 H210 H212 A second aspect of the present application provides a pharmaceutical composition, comprising the compound of formula (I) according to the first aspect of the present application, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof; and a pharmaceutically acceptable carrier. A third aspect of the present application provides use of the compound of formula (I) according to 5 the first aspect of the present application, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or the pharmaceutical composition according to the second aspect of the present application, in the manufacture of a medicament for preventing and / or treating an EED-mediated disease. In some embodiments, the EED-mediated disease is a tumor or an autoimmune disease. In some embodiments, the EED-mediated disease is cancer. In some embodiments, the cancer is selected from the group consisting of multiple myeloma, leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer. A fourth aspect of the present application provides a method for preventing and / or treating an EED-mediated disease, comprising administering a therapeutically effective amount of the compound of formula (I) according to the first aspect of the present application, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or the pharmaceutical composition according to the second aspect of the present application to a subject. In some embodiments, the EED-mediated disease is a tumor or an autoimmune disease. In some embodiments, the EED-mediated disease is cancer. In some embodiments, the cancer is selected from the group consisting of multiple myeloma, leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings described herein are intended to provide a further understanding of the present application and constitute a part of the present application. The schematic embodiments and descriptions thereof in the present application are intended to explain the present application and do not constitute an undue limitation on the present application. FIG. 1 is a graph showing the in vivo antitumor activity results of Compound D1 and Compound H105; FIG. 2 is a graph showing the effect of Compound D1 and Compound H105 on mouse body weight. DETAILED DESCRIPTION After extensive and in-depth research, the present inventors have unexpectedly discovered a bifunctional compound targeting degradation and / or inhibition of EED protein. This compound exhibits excellent EED protein degradation activity, excellent tumor cell (such as wsuDLCL-2 cells, Pfeiffer cells, etc.) proliferation inhibitory activity, excellent pharmacokinetic properties, excellent CYP450 profile, and good safety, making it more suitable for the treatment of diseases or conditions associated with abnormal EED protein activity (such as proliferative diseases like cancer). Based on this, the inventors have completed the present application. Definition of Terms In order to more clearly understand the technical content of the present application, the terms of the present application are further described below. The present application provides a bifunctional compound or PROTAC compound, which has a structure of POI—ULM or a structure of POI—L—ULM, wherein POI is a ligand targeting EED protein (or a ligand that binds to EED protein), ULM is an E3 ligase binding group (or a binding group), and L is a linker connecting POI and ULM. The PROTAC compound can bind to EED protein through the POI moiety, thereby bringing EED protein into proximity with an E3 ligase, thus inducing degradation (and / or inhibition) of EED protein. Commonly used E3 ligase ligands include VHL (Von Hippel-Lindau) E3 ubiquitin ligase binding group (abbreviated as VLM), CRBN (cereblon) E3 ubiquitin ligase binding group (abbreviated as CLM), MDM2 (mouse double minute 2 homologue) E3 ubiquitin ligase binding group (abbreviated as MLM), cIAP (cellular inhibitor of apoptosis) E3 ubiquitin ligase binding group (abbreviated as ILM), and the like. POI is a ligand targeting EED protein and can bind to EED protein. “Alkyl” refers to linear and branched saturated aliphatic hydrocarbon groups. “C1-10 alkyl” refers to an alkyl group having 1 to 10 carbon atoms, preferably C1-8 alkyl; more preferably C1-6 alkyl; further preferably C1-3 alkyl. Non-limiting examples of alkyl include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched isomers thereof. “Alkenyl” refers to linear or branched unsaturated aliphatic hydrocarbon groups having one or more carbon-carbon double bonds (C=C). “C2-10 alkenyl” refers to an alkenyl group having 2 to 10 carbon atoms, preferably C2-8 alkenyl, more preferably C2-6 alkenyl, further preferably C2-4 alkenyl, with a similar definition. Non-limiting examples of alkenyl include vinyl, propenyl, isopropenyl, n-butenyl, isobutenyl, pentenyl, hexenyl, and the like. “Alkynyl” refers to linear and branched unsaturated aliphatic hydrocarbon groups having one or more carbon-carbon triple bonds. “C2-10 alkynyl” refers to an alkynyl group having 2 to 10 carbon atoms, preferably C2-8 alkynyl, more preferably C2-6 alkynyl, further preferably C2-4 alkynyl, with a similar definition. Non-limiting examples of alkynyl include ethynyl, propynyl, n-butynyl, isobutynyl, pentynyl, hexynyl, and the like. “Alkylene” is divalent and requires two binding partners. Formally, the second valence is generated by removing a hydrogen atom from an alkyl group, such as -CH3 and -CH2-, -CH2CH3 and -CH2CH2- or -CH(CH3)-, and the like. In certain embodiments, C1-10 alkylene is preferred, more preferably C1-8 alkylene, further preferably C1-6 alkylene, most preferably C1-3 alkylene. For example, C1-3 alkylene includes -CH2-, -(CH2)2-, -CH(CH3)-, -(CH2)3-, -CH(CH2CH3)-, -CH2CH(CH3)- and -C(CH3)2-. In certain embodiments, alkylene can be methylene, ethylene, propylene, 1-methylethylene, butylene,      1-methylpropylene1,1-dimethylethylene,      1,2-dimethylethylene,      pentylene, 1,1-dimethylpropylene, 2,2-dimethylpropylene, 1,2-dimethylpropylene, 1,3-dimethylpropylene, and the like. In the absence of any further definition, the generic terms propylene, butylene, pentylene, hexylene, etc., refer to all conceivable isomeric forms having the corresponding number of carbon atoms, i.e., propylene includes 1-methylethylene, and butylene includes 1-methylpropylene, 2-methylpropylene, 1,1-dimethylethylene and 1,2-dimethylethylene. “Alkenylene” consists of at least two carbon atoms, wherein at least two adjacent carbon atoms are connected by a C-C double bond, and the carbon atoms can be part of only one C-C double bond. Formally, in the alkylene defined above, if two hydrogen atoms on adjacent carbon atoms are formally removed and the free valences are saturated to form a second bond, the corresponding alkenylene is formed. In certain embodiments, C2-10 alkenylene is preferred, more preferably C2-8 alkenylene, further preferably C2-6 alkenylene, most preferably C2-4 alkenylene. In certain embodiments, alkenylene can be ethenylene,     propenylene,      1-methylethenylene,     butenylene,      1-methylpropenylene, 1,1-dimethylethenylene,     1,2-dimethylethenylene,     pentenylene,     1,1-dimethylpropenylene, 2,2-dimethylpropenylene, 1,2-dimethylpropenylene, 1,3-dimethylpropenylene, hexenylene, and the like. In the absence of any further definition, the generic terms propenylene, butenylene, pentenylene, hexenylene, etc., refer to all conceivable isomeric forms having the corresponding number of carbon atoms, i.e., propenylene includes 1-methylpropenylene, and butenylene includes 1-methylpropenylene, 2-methylpropenylene, 1,1-dimethylethenylene and 1,2-dimethylethenylene. For one or more double bonds, alkenylene may optionally exist in cis or trans, or E or Z forms. “Alkynylene” consists of at least two carbon atoms, wherein at least two adjacent carbon atoms are connected by a C-C triple bond. Formally, in the alkylene defined above, if two hydrogen atoms are removed from two adjacent carbon atoms and the free valences are saturated to form two additional bonds, the corresponding alkynylene is formed. In certain embodiments, C2-10 alkynylene is preferred, more preferably C2-8 alkynylene, further preferably C2-6 alkynylene, most preferably C2-4 alkynylene. In certain embodiments, alkynylene can be ethynylene, propynylene, 1-methylethynylene, butynylene, 1-methylpropynylene,      1,1-dimethylethynylene,      1,2-dimethylethynylene,      pentynylene, 1,1-dimethylpropynylene,            2,2-dimethylpropynylene,            1,2-dimethylpropynylene, 1,3-dimethylpropynylene, hexynylene, and the like. In the absence of any further definition, the generic terms propynylene, butynylene, pentynylene, hexynylene, etc., refer to all conceivable isomeric forms having the corresponding number of carbon atoms, i.e., propynylene includes 1-methylethynylene, and butynylene includes 1-methylpropynylene, 2-methylpropynylene, 1,1-dimethylethynylene and 1,2-dimethylethynylene. “Alkyleneoxy” refers to a divalent alkoxy group. In certain embodiments, C1-10 alkyleneoxy is preferred, more preferably C1-8 alkyleneoxy, further preferably C1-6 alkyleneoxy, most preferably C1-3 alkyleneoxy. In certain embodiments, alkyleneoxy can be -OCH2-, -OCH(CH3)CH2-, -OCH2CH2O-, -CH2CH2O-, and the like. In the absence of any further definition, the generic terms propyleneoxy, butyleneoxy, pentyleneoxy, hexyleneoxy, etc., refer to all conceivable isomeric forms having the corresponding number of carbon atoms, i.e., propyleneoxy includes -O(CH2)3O-, -O(CH2)3-, -OCH2CH(CH3)-,   -OC(CH3)2-,   -OCH(CH3)CH2-, -OCH2CH(CH3)O-, -OC(CH3)2O-   and -OCH(CH3)CH2O-. “Cycloalkyl” and “cycloalkyl ring” are used interchangeably and both refer to a monocyclic or polycyclic cyclic hydrocarbon group, which may be fused to an aryl or heteroaryl group. The cycloalkyl ring may be optionally substituted. In certain embodiments, the cycloalkyl ring includes one or more of spiro rings and bridged rings. In certain embodiments, the cycloalkyl ring contains one or more carbonyl groups, such as oxo groups. “C3-15 cycloalkyl” refers to a monocyclic or polycyclic cycloalkyl group having 3 to 15 carbon atoms, such as spiro[4.5]decane, spiro[3.3]heptane, spiro[5.5]undecane, dispiro[5.2.59.26]hexadecane, decahydroazulene, 1,2-diethylcyclopent-1-ene, bicyclo[3.3.2]decane. Preferred are C3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclobutanone, cyclopentanone, cyclopentane-1,3-dione, and the like. Preferred are C3-7 cycloalkyl, such as cycloheptane, spiro[3.3]heptane, etc., more preferably C3-6 cycloalkyl, including cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. It can be a saturated cycloalkyl, such as cyclohexyl, cyclopropyl, etc. It can be a partially unsaturated cycloalkyl, such as cyclohexene, 1,2-diethylcyclopent-1-ene, etc. “Spiro ring” refers to a polycyclic group in which single rings share one carbon atom (called the spiro atom), which may contain one or more double bonds, but no ring has a fully conjugated n-electron system. Spiro rings are classified as dispiro rings or polyspiro rings based on the number of rings, with dispiro rings being preferred. More preferred are 4-membered / 5-membered, 5-membered / 5-membered or 5-membered / 6-membered dispiro rings. For example: . “Cycloalkylene” and “cycloalkylene ring” are used interchangeably, both are divalent and require two binding partners. Formally, the second valence is generated by removing a hydrogen atom from a cycloalkyl group, for example      . “Spiro-heterocycle” refers to a polycyclic hydrocarbon in which single rings share one atom (referred to as the spiro atom), wherein one or two ring atoms are heteroatoms selected from nitrogen, oxygen or S(O)n (wherein n is an integer from 0 to 2), and the remaining ring atoms are carbon, which may contain one or more double bonds, but no ring has a fully conjugated n-electron system. Spiroheterocycles are classified as dispiroheterocycles or polyspiroheterocycles based on the number of rings, with dispiroheterocycles being preferred. More preferred are 4-membered / 5-membered, 5-membered / 5-membered or 5-membered / 6-membered dispiroheterocycles. For example: “Bridged ring” refers to a polycyclic group in which two or more carbon atoms are shared. The shared carbon atoms are referred to as bridgehead carbons, and between two bridgehead carbons there may be a carbon chain or a single bond, which is referred to as a bridge. These may contain one or 5 more double bonds, but no ring has a fully conjugated n-electron system. Preferred are bicyclic or tricyclic bridged rings. For example: “Bridged heterocycle” refers to a polycyclic group in which two or more atoms are shared, 10 wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen or S(O)n (wherein n is an integer from 0 to 2), and the remaining ring atoms are carbon. These may contain one or more double bonds, but no ring has a fully conjugated n-electron system. Preferred are bicyclic or tricyclic bridged heterocycles. For example: 15        “Heterocycloalkyl” and “heterocycloalkyl ring” are used interchangeably, both refer to a cycloalkyl group containing at least one heteroatom selected from nitrogen, oxygen and sulfur, and the group may be fused to an aryl or heteroaryl group. The heterocycloalkyl ring may be a saturated heterocycloalkyl ring or a partially unsaturated heterocycloalkyl ring. The heterocycloalkyl ring may be optionally substituted. In certain embodiments, the heterocycloalkyl ring includes one or more of spiro-heterocycles and bridged heterocycles. In certain embodiments, the heterocycloalkyl ring contains one or more carbonyl or thiocarbonyl groups, such as groups containing oxo and thio. “3- to 15-membered heterocycloalkyl” refers to a heterocycloalkyl group having 3 to 15 ring atoms, wherein 1, 2 or 3 ring atoms are heteroatoms selected from nitrogen, oxygen and sulfur. Preferred are 3- to 10-membered heterocycloalkyl, more preferably 3- to 7-membered heterocycloalkyl, further more preferably 3- to 7-membered heterocycloalkyl, further preferably 3- to 6-membered heterocycloalkyl. Non-limiting examples of heterocycloalkyl include aziridinyl, oxiranyl, azetidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyrrolyl, oxazolidinyl, dioxolanyl, piperidinyl, piperazinyl, morpholinyl, dioxanyl, thiomorpholinyl, thiomorpholine-1,1-dioxide, tetrahydropyranyl, azetidin-2-onyl, oxetan-2-onyl, dihydrofuran-2(3H)-onyl, pyrrolidin-2-onyl, pyrrolidine-2,5-dionyl, dihydrofuran-2,5-dionyl, piperidin-2-onyl, tetrahydro-2H-pyran-2-onyl, piperazin-2-onyl, morpholin-3-onyl,        2,3-dihydrofuran,        2,5-dihydrofuran,        2,5-dihydro-1H-pyrrole, 1,2,3,4-tetrahydropyridine, 1,2,3,6-tetrahydropyridine, and the like. “Heterocycloalkylene” and “heterocycloalkylene ring” are used interchangeably, both are divalent and require two binding partners. Formally, the second valence is generated by removing a hydrogen atom from a cycloalkyl group, for example ' . “Aryl” and “aryl ring” are used interchangeably, both refer to a group of a monocyclic, bicyclic or polycyclic 4n+2 aromatic ring system having ring carbon atoms (e.g., having 6 or 10, or 14 n electrons shared in a cyclic arrangement). In the present application, the aryl ring may be optionally substituted. “C6-14 aryl” refers to an aryl group having 6 to 14 ring carbon atoms. “C6-10 aryl” refers to an aryl group having 6 to 10 ring carbon atoms. Non-limiting examples include phenyl, naphthyl and anthracenyl. “Arylene” and “arylene ring” are used interchangeably, both are divalent and require two binding partners. Formally, the second valence is generated by removing a hydrogen atom from a cycloalkyl f 1 jb group, for example “Heteroaryl” and “heteroaryl ring” are used interchangeably, both refer to a group of a monocyclic, bicyclic or polycyclic 4n+2 aromatic ring system having ring carbon atoms and ring heteroatoms (e.g., having 6 or 10 or 14 n electrons shared in a cyclic arrangement), wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur. In the present application, heteroaryl also includes ring systems in which the aforementioned heteroaryl ring is fused to one or more cycloalkyl rings, heterocycloalkyl rings, cycloalkenyl rings, heterocycloalkenyl rings or aryl rings. The heteroaryl ring may be optionally substituted. “5- to 15-membered heteroaryl” refers to a monocyclic heteroaryl having 5 to 15 ring atoms, wherein 1, 2, 3 or 4 ring atoms are heteroatoms. “5-to 6-membered heteroaryl” refers to a monocyclic heteroaryl having 5 to 6 ring atoms, wherein 1, 2, 3 or 4 ring atoms are heteroatoms. Non-limiting examples include thienyl, furyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, benzopyrrolyl, benzofuranyl, benzothienyl, benzopyrazolyl, benzimidazolyl, benzotriazolyl, benzotetrazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzothiadiazolyl, pyridopyrrolyl, pyridofuranyl, pyridothienyl, pyridopyrazolyl, pyridoimidazolyl, pyridotriazolyl, pyridotetrazolyl, pyridooxazolyl, pyridoisoxazolyl, pyridooxadiazolyl, pyridothiazolyl, pyridothiadiazolyl, pyrimidopyrrolyl, pyrimidofuranyl, pyrimidothienyl, pyrimidopyrazolyl, pyrimidoimidazolyl, pyrimidotriazolyl, pyrimidotetrazolyl, pyrimidooxazolyl, pyrimidoisoxazolyl, pyrimidooxadiazolyl, pyrimidothiazolyl, pyrimidothiadiazolyl, pyridazopyrrolyl, pyridazofuranyl, pyridazothienyl, pyridazopyrazolyl, pyridazoimidazolyl, pyridazotriazolyl, pyridazotetrazolyl, pyridazooxazolyl, pyridazoisoxazolyl, pyridazooxadiazolyl, pyridazothiazolyl, pyridazothiadiazolyl, pyrazinopyrrolyl, pyrazinofuranyl, pyrazinothienyl, pyrazinopyrazolyl, pyrazinoimidazolyl, pyrazinotriazolyl, pyrazinotetrazolyl, pyrazinooxazolyl, pyrazinoisoxazolyl, pyrazinooxadiazolyl, pyrazinothiazolyl, pyrazinothiadiazolyl, triazinopyrrolyl, triazinofuranyl, triazinothienyl, triazinopyrazolyl, triazinoimidazolyl, triazinotriazolyl, triazinotetrazolyl, triazinooxazolyl, triazinoisoxazolyl, triazinooxadiazolyl, triazinothiazolyl, triazinothiadiazolyl, benzoquinolinyl, benzoisoquinolinyl and carbazolyl. “Heteroatom” refers to nitrogen, oxygen or sulfur. In a heteroaryl containing one or more nitrogen atoms, the point of attachment may be a carbon or nitrogen atom, provided that the valence allows. A heteroaryl bicyclic system may include one or more heteroatoms in one or two rings. “Heteroarylene” and “heteroarylene ring” are used interchangeably, both are divalent and require two binding partners. Formally, the second valence is generated by removing a hydrogen atom from a d cycloalkyl group, for example ■ . “Halogen” refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I). “Halo” refers to the substitution of one or more (e.g., 1, 2, 3 or all) hydrogen atoms in a group with halogen. “Haloalkyl” refers to an alkyl group substituted with one or more (e.g., 1, 2, 3 or all) halogen atoms, wherein alkyl is as defined above. Preferred are C1-8 haloalkyl, more preferably C1-6 haloalkyl, even more preferably C1-3 haloalkyl. Examples of haloalkyl include, but are not limited to, chloromethyl, dichloromethyl, trichloromethyl, chloroethyl, 1,2-dichloroethyl, trichloroethyl, bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, and the like. “Alkoxy” refers to -O-alkyl, wherein alkyl is as defined above. Preferred are C1-8 alkoxy, more preferably C1-6 alkoxy, most preferably C1-3 alkoxy. Non-limiting examples of alkoxy include methoxy, ethoxy, n-propoxy, isopropoxy, butoxy, tert-butoxy, isobutoxy, pentyloxy, and the like. “Alkoxyalkyl” refers to an alkyl group substituted with one or more alkoxy groups, wherein alkyl and alkoxy are as defined above. Preferred are C1-6 alkoxy C1-6 alkyl, more preferably C1-3 alkoxy C1-3 alkyl. Non-limiting examples of alkoxyalkyl include -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, and the like. “Cycloalkylalkyl” refers to an alkyl group substituted with one or more cycloalkyl groups, wherein alkyl and cycloalkyl are as defined above. Preferred are C3-6 cycloalkyl C1-6 alkyl, more preferably C3-6 cycloalkyl C1-3 alkyl. Non-limiting examples of cycloalkylalkyl include -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclobutyl, and the like. “Alkenylalkyl” refers to an alkyl group substituted with one or more alkenyl groups, wherein alkyl and alkenyl are as defined above. Preferred are C2-8 alkenyl C1-10 alkyl, more preferably C2-8 alkenyl C1-8 alkyl, further preferably C2-8 alkenyl C1-6 alkyl, further preferably C2-8 alkenyl C1-3 alkyl. —ch2ch3 Non-limiting examples of cycloalkylalkyl include-H2C-HC=CH2, —ch2ch2—hc=ch2,   hc ch2, and the like. “Alkynylalkyl” refers to an alkyl group substituted with one or more alkynyl groups, wherein alkyl and alkynyl are as defined above. Preferred are C2-8 alkynyl C1-10 alkyl, more preferably C2-8 alkynyl C1-8 alkyl, further preferably C2-8 alkynyl C1-6 alkyl, further preferably C2-8 alkynyl C1-3 alkyl. —ch2ch3 Non-limiting examples of cycloalkylalkyl include , — H2C c=ch , —ch2ch2 c=ch , c=ch , and the like. “Heterocycloalkylalkyl” refers to an alkyl group substituted with one or more heterocycloalkyl groups, wherein alkyl and heterocycloalkyl are as defined above. Preferred are 4- to 10-membered heterocycloalkyl C1-6 alkyl, more preferably 4- to 8-membered heterocycloalkyl C1-3 alkyl, further preferably 3- to 6-membered heterocycloalkyl C1-3 alkyl, further preferably 4- to 6-membered heterocycloalkyl C1-3 alkyl. Non-limiting examples of heterocycloalkylalkyl include -CH2-tetrahydropyrrolyl, -CH2-azetidinyl, -CH2-piperidinyl, -CH2-piperazinyl, and the like. “Hydroxy-substituted alkyl” refers to an alkyl group substituted with one or more hydroxyl groups, wherein alkyl is as defined above. Preferred are hydroxy-substituted C1-10 alkyl, more preferably hydroxy-substituted C1-8 alkyl, further preferably hydroxy-substituted C1-6 alkyl, even more preferably hydroxy-substituted C1-3 alkyl. Non-limiting examples of “hydroxy-substituted alkyl” include -CH2OH, -CH2CH2OH, -CH(OH)CH3, and the like. “Cyano-substituted alkyl” refers to an alkyl group substituted with one or more cyano groups, wherein alkyl is as defined above. Preferred are cyano-substituted C1-10 alkyl, more preferably cyano-substituted C1-8 alkyl, further preferably cyano-substituted C1-6 alkyl, further preferably cyano-substituted C1-3 alkyl. Non-limiting examples of “cyano-substituted alkyl” include -CH2CN, -CH2CH2CN, -CH(CN)CH3, and the like. “Carboxy-substituted alkyl” refers to an alkyl group substituted with one or more carboxy groups, wherein alkyl is as defined above. Preferred are carboxy-substituted C1-10 alkyl, more preferably carboxy-substituted C1-8 alkyl, further preferably carboxy-substituted C1-6 alkyl, further preferably carboxy-substituted C1-3 alkyl. Non-limiting examples of “carboxy-substituted alkyl” include -CH2COOH, -CH2CH2COOH, -CH(COOH)CH3, and the like. “Amino-substituted alkyl” refers to an alkyl group substituted with one or more amino groups, wherein alkyl is as defined above. Preferred are amino-substituted C1-10 alkyl, more preferably amino-substituted C1-8 alkyl, further preferably amino-substituted C1-6 alkyl, further preferably amino-substituted C1-3 alkyl. Non-limiting examples of “amino-substituted alkyl” include -CH2NH2, -CH2CH2NH2, -CH(NH2)CH3, and the like. “Haloalkoxy” refers to an alkoxy group substituted with one or more (e.g., 1, 2, 3, 4 or 5) halogen atoms, wherein alkoxy is as defined above. Preferred are C1-10 haloalkoxy, more preferably C1-8 haloalkoxy, further preferably C1-6 haloalkoxy, further preferably C1-3 haloalkoxy. Haloalkoxy includes, but is not limited to, trifluoromethoxy, trifluoroethoxy, monofluoromethoxy, monofluoroethoxy, difluoromethoxy, difluoroethoxy, and the like. “Amino” refers to -NH2, “cyano” refers to -CN, “nitro” refers to -NO2, “benzyl” refers to -CH2-phenyl, “oxo” refers to =O, “carboxy” refers to -C(O)OH, “acetyl” refers to -C(O)CH3, “acetamido” refers to -C(O)NH2, “hydroxymethyl” refers to -CH2OH, “hydroxyethyl” refers to -CH2CH2OH or -CHOHCH3, “hydroxyl” refers to -OH, “thiol” refers to -SH; “formyl” refers to -CHO; “sulfo” refers to -SO3H. As defined in the present application, “when R2 or R3 is X1, X1 is the point of attachment of POI to L or ULM” means that POI is connected to L or ULM via a covalent connection, and X1 is the point of attachment to L or ULM. For the compound of formula (I), when POI is structure and X1 represents the point of attachment to L or ULM, its meaning is the same when n0 is 0 or 1. Similarly, for the compound of wherein X2 is the point of attachment of ULM to L or POI, its meaning is the same as that expressed by (LJno-PO1, when n0 is 0 or 1. “Substituted” means that one or more hydrogen atoms in a group, preferably 1 to 5 hydrogen atoms, are independently replaced by a corresponding number of substituents, more preferably 1 to 3 hydrogen atoms are independently replaced by a corresponding number of substituents. It goes without saying that substituents are only present at their chemically possible positions, and a person skilled in the art can determine (through experimentation or theory) possible or impossible substitutions without undue effort. For example, an amino or hydroxyl group having a free hydrogen may be unstable when bonded to a carbon atom having an unsaturated (e.g., ethylenic) bond. When the number of substituents is not indicated in this application, it means that substitution can be carried out with an optional substitutable number of substituents. Unless otherwise defined, “substituents each independently selected from ...” in this application means that when more than one hydrogen on a group is replaced by substituents, the types of said substituents can be the same or different, and the selected substituents are each independent types. Unless otherwise defined, any group herein can be substituted or unsubstituted. When the above group is substituted, the substituents are preferably 1 to 5 groups independently selected from the group consisting of deuterium, halogen (preferably fluorine, chlorine), cyano, hydroxyl, carboxyl, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), C2-4 alkenyl, C2-4 alkynyl, C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl), cyano-substituted C1-8 alkyl (preferably cyano-substituted C1-6 alkyl, more preferably cyano-substituted C1-3 alkyl), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy), NRA0RB0, -SO2C1-3 alkyl, -S(O)C1-3 alkyl, -C(O)NRA10RB10, -C(O)C1-8 alkyl (preferably -C(O)C1-6 alkyl, more preferably -C(O)C1-3 alkyl), -C(O)OC1-8 alkyl (preferably -C(O)OC1-6 alkyl, more preferably -C(O)OC1-3 alkyl), -OC(O)C1-8 alkyl (preferably -OC(O)C1-6 alkyl, more preferably -OC(O)C1-3  alkyl), C3-6 cycloalkyl, C3-6 cycloalkyloxy,  3- to 6-membered heterocycloalkyl, phenyl and 5- to 6-membered heteroaryl; wherein the 3- to 6-membered heterocycloalkyl, phenyl and 5- to 6-membered heteroaryl in the substituents are unsubstituted or substituted with 1, 2 or 3 groups each independently selected from the group consisting of halogen, cyano, hydroxyl, carboxyl, C1-3 alkyl, C1-3 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-3 haloalkyl, C1-3 haloalkoxy, NRA0RB0, -SO2C1-3 alkyl, -S(O)C1-3 alkyl, -C(O)NRA10RB10, -C(O)OC1-3 alkyl, -OC(O)C1-3 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyloxy, 3- to 6-membered heterocycloalkyl, phenyl and 5- to 6-membered heteroaryl. RA10 and RB10 are each independently hydrogen or C1-3 alkyl; or RA10, RB10 and nitrogen atom linked to RA10 and RB10 together form a 4- to 6-membered saturated monocyclic heterocycle; the 4- to 6-membered saturated monocyclic heterocycle is unsubstituted or substituted with 1, 2 or 3 substituents each independently selected from the group consisting of deuterium, halogen, cyano, hydroxyl, carboxyl, C1-3 alkyl, C1-3 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-3 haloalkyl, C1-3 haloalkoxy, -SO2C1-3 alkyl, -S(O)C1-3 alkyl, -C(O)NH2, -C(O)NH(C1-3 alkyl), -C(O)N(C1-3 alkyl)2, -C(O)OC1-3 alkyl, -OC(O)C1-3 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyloxy and 3- to 6-membered heterocycloalkyl; RA0 and RB0 are each independently hydrogen, C1-3 alkyl or acetyl; or RA0, and RB0 and nitrogen atom linked to RA0 and RB0 together form a 4- to 6-membered saturated monocyclic heterocycle; the 4-to 6-membered saturated monocyclic heterocycle is unsubstituted or substituted with 1, 2 or 3 substituents each independently selected from the group consisting of deuterium, halogen, cyano, hydroxyl, carboxyl, C1-3 alkyl, C1-3 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-3 haloalkyl, C1-3 haloalkoxy, -SO2C1-3 alkyl, -S(O)C1-3 alkyl, -C(O)NH2, -C(O)NH(C1-3 alkyl), -C(O)N(C1-3 alkyl)2, -C(O)OC1-3 alkyl, -OC(O)C1-3 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyloxy and 3- to 6-membered heterocycloalkyl. In this application, when two or more “preferably” appear in one scheme, any two “preferably” can be independent of each other. In this application, when the number of substituents is greater than 1, any two substituents can be the same or different. For example, it can be two identical or different halogen substitutions, or one halogen and one hydroxy substitution. Each of the various substituent groups described above can itself be substituted with the groups described herein. Pharmaceutical Composition Generally, the compound of the present application or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, can be formulated into a suitable dosage form with one or more pharmaceutical carriers for administration. These dosage forms are suitable for oral, rectal, topical, buccal administration, and other parenteral administration (e.g., subcutaneous, intramuscular, intravenous, etc.). For example, dosage forms suitable for oral administration include capsules, tablets, granules, syrups, and the like. “Pharmaceutically acceptable carrier” refers to a non-toxic, inert, solid, semi-solid substance or liquid filler, diluent, encapsulating material, or auxiliary formulation, or any type of excipient, which is compatible with the patient, preferably a mammal, more preferably a human, and is suitable for delivering the active agent to the target site without terminating the activity of the agent. The compositions of the present application are formulated, dosed, and administered in a manner consistent with good medical practice. A “therapeutically effective amount” of the compound to be administered is determined by factors such as the specific condition being treated, the individual being treated, the cause of the condition, the target of the drug, and the mode of administration. “Therapeutically effective amount” refers to an amount of the compound of the present application that will elicit a biological or medical response in an individual, for example, reducing or inhibiting enzyme or protein activity, or ameliorating symptoms, alleviating conditions, slowing or delaying disease progression, or preventing disease, etc. “Patient” refers to an animal, preferably a mammal, more preferably a human. The term “mammal” refers to warm-blooded vertebrate mammals, including, for example, cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, mice, pigs, and humans. “Treatment” refers to alleviating, delaying progression, attenuating, preventing, or maintaining an existing disease or condition (e.g., cancer). Treatment also includes curing one or more symptoms of a disease or condition, preventing its development, or alleviating it to some extent. “Pharmaceutically acceptable salt” includes pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. “Pharmaceutically acceptable acid addition salt” refers to a salt formed with an inorganic or organic acid that retains the biological effectiveness of the free base without other side effects. “Pharmaceutically acceptable base addition salt” includes, but is not limited to, salts of inorganic bases and salts of organic bases. The compounds of the present application may contain one or more chiral centers and exist in different optically active forms. When the compound contains one chiral center, the compound includes enantiomers. When the compound contains more than one chiral center, diastereomers may exist. The present application includes both of these stereoisomers as well as mixtures of these two stereoisomers, such as racemates, diastereomeric mixtures, and the like. Unless otherwise indicated, a wedge bond     or '''' is used to indicate the absolute configuration of a stereocenter. When the compounds described herein contain olefinic double bonds or other geometric asymmetry centers, unless otherwise specified, they include E and Z geometric isomers. Likewise, all tautomeric forms are included within the scope of the present application. The enantiomers, diastereomers, and mixtures of these isomers of the compounds of the present application are within the protection scope of the present invention. Enantiomers and diastereomers can be resolved by methods known in the art, such as crystallization and chiral chromatography. Preparation Methods The present application provides methods for preparing the compounds of formula (I). The compounds of formula (I) can be synthesized using standard synthetic techniques known to those skilled in the art, or using methods known in the art in combination with the methods described herein. The solvents, temperatures, and other reaction conditions given herein can be varied according to the knowledge in the art. The reactions can be used sequentially to provide the compounds of the present application, or they can be used to synthesize fragments that are subsequently added by methods described herein and / or known in the art. For the reactions in the above schemes, a person skilled in the art can make adaptive adjustments with reference to the specific examples described in this application or based on existing literature, according to the properties of the participating reactants, without causing difficulty to those skilled in the art. The compounds described in this application can be synthesized using methods analogous to those described below or the exemplary methods in the Examples, or relevant published literature used by those skilled in the art, by using appropriate alternative starting materials. Starting materials or intermediates used to synthesize the compounds described in this application can be synthesized or obtained from commercial sources. If not reported in existing literature or not available commercially, they can be prepared using similar existing preparation methods for analogous compounds or similar preparation methods described in this application. The compounds described in this application and other related compounds with different substituents can be synthesized using techniques and starting materials known to those skilled in the art. General methods for preparing the compounds disclosed in this application can be derived from reactions known in the art, and the reactions can be modified by reagents and conditions deemed appropriate by those skilled in the art to introduce various moieties into the molecules provided herein. Compared with the prior art, the main advantages of the present application are: the compound of the present application have excellent EED protein degradation effects and tumor cell proliferation inhibitory effects, and have excellent pharmacokinetic properties, excellent effects on cytochrome P450, good safety, and are more suitable for treating diseases or conditions with abnormal EED protein activity (such as proliferative diseases like cancer) . The present application is further described below in conjunction with specific examples. It 5 should be understood that these examples are only intended to illustrate the present application and are not intended to limit the scope of the present application. In the following examples, where specific conditions are not indicated for the experimental methods, they were usually carried out under conventional conditions such as those described in Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989), or according to the conditions 10 recommended by the manufacturer. Unless otherwise indicated, percentages and parts are calculated by weight. Unless otherwise defined, terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described can be applied in the present application. Reagents and Instruments 15       1H NMR: Bruker AVANCE-400 nuclear magnetic resonance instrument, with tetramethylsilane (TMS) as internal standard. LC-MS: Agilent 1290 HPLC System / 6130 / 6150 MS LC-MS mass spectrometer (manufacturer: Agilent), column Waters BEH / CHS, 50 x 2.1 mm, 1.7 gm. Preparative High-Performance Liquid Chromatography (pre-HPLC): GX-281 (manufacturer: 20 Gilson). ISCO Combiflash-Rf75 or Rf200 automatic column chromatography instrument was used, with Agela 4 g, 12 g, 20 g, 40 g, 80 g, 120 g disposable silica gel columns. Known starting materials can be synthesized using or according to methods known in the art, or can be purchased from companies such as ABCR GmbH & Co. KG, Acros Organics, Aldrich 25 Chemical Company, Accela ChemBio Inc., and Darui Chemicals. In the examples, the progress of reactions can be monitored using thin layer chromatography (TLC), and compound purification can be performed using column chromatography. The developing solvent systems used for column chromatography or TLC can be selected from dichloromethane and methanol systems, n-hexane and ethyl acetate systems, petroleum ether and ethyl acetate systems, and 30 acetone systems, etc. The volume ratio of solvents is adjusted according to the polarity of the compound. As used herein, PE: petroleum ether, EA: ethyl acetate, THF: tetrahydrofuran, H2O: water, DMF: N,N-dimethylformamide, DCM: dichloromethane, MeOH: methanol, EtOH: ethanol, DMSO: dimethyl sulfoxide, DCE: 1,2-dichloroethane, NMP: N-methylpyrrolidone, DME: dimethyl ether, DMAC: 35 N,N-dimethylacetamide, TFA: trifluoroacetic acid, FA: formic acid, AcOH: acetic acid, CH3COOH: acetic acid, SOCl2: thionyl chloride, POCl3: phosphorus oxychloride, PCy3: tricyclohexylphosphine, Et3N: triethylamine, LiOH: lithium hydroxide, LiAlH4: lithium aluminum hydride, NaOH: sodium hydroxide, NaHCO3: sodium bicarbonate, NaH: sodium hydride, KOAc: potassium acetate, K2CO3: potassium carbonate, Cs2CO3: cesium carbonate, NH4HCO3: ammonium bicarbonate, TCFH: N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate, HATU: 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, HOBT:   1-hydroxybenzotriazole, EDCI: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, Pd(dppf)Cl2: [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium(II); DIPEA: N,N-diisopropylethylamine, mCPBA: meta-chloroperoxybenzoic acid, Pd(PPh3)4:    tetrakis(triphenylphosphine)palladium(0),    Pd2(dba)3:    tris(dibenzylideneacetone) dipalladium(0), Pd(dba)2: bis(dibenzylideneacetone)palladium(0), Pd(OAc)2: palladium(II) acetate, Xantphos:  4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, NIS:  N-iodosuccinimide, NBS: N-bromosuccinimide, CuI:   copper(I) iodide,  PPh3:  triphenylphosphine, DEAD:   diethyl azodicarboxylate, NaBH3CN: sodium cyanoborohydride, NaBH(OAc)3: sodium triacetoxyborohydride, B2Pin2:   bis(pinacolato)diboron, X-Phos:   2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, Selectfluor: 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), Ruphos-Pd-G3:   methanesulfonato(2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2'-amino-1,1'- biphenyl-2-yl)palladium(II),      DIBAL-H:      diisobutylaluminum      hydride,      DIEA: N,N-diisopropylethylamine, DMAP: 4-dimethylaminopyridine, Ruphos: 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl, LiHMDS: lithium bis(trimethylsilyl)amide, TEA: triethylamine, MeCN: acetonitrile, Boc2O: di-tert-butyl dicarbonate, Dess-Martin periodinane: Dess-Martin periodinane,    (Pin)2B2:    bis(pinacolato)diboron, n-BuLi:    n-butyllithium,    Pd(PPh3)2Cl2: bis(triphenylphosphine)palladium(II) dichloride, t-BuOH:   tert-butanol, DIAD:   diisopropyl azodicarboxylate,       TBSCl:       tert-butyldimethylchlorosilane,       CataCXium       A: n-butylbis(1-adamantyl)phosphine, RhCl(PPh3)3: chlorotris(triphenylphosphine)rhodium(I), TsOH: p-toluenesulfonic       acid,       PtO2:       platinum(IV)       oxide,       Pd(aMphos)Cl2: dichlorobis(di-tert-butyl(4-dimethylaminophenyl)phosphine)palladium(II). Regarding the percentage contents involved herein, unless otherwise specified, for solid-liquid mixtures and solid-solid mixtures, they refer to mass percentages; for liquid-liquid mixtures, they refer to volume percentages. Unless otherwise specified, the solvent is water. As used herein, r.t. indicates room temperature, which refers to approximately 20°C to 30°C. As used herein, “overnight” means approximately 10 h to 16 h. Preparation of Intermediate Z1 Step 1: 8-Bromo-5-(methylthio)-[1,2,4]triazolo[4,3-c]pyrimidine (5 g, 20.40 mmol) and (5-fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (5 g, 29.91 mmol) were mixed, pre-sonicated for 5 minutes, and then stirred at 85°C for 3 hours under microwave irradiation. After the reaction was complete, DCM (100 mL) was added, followed by sonication and filtration. The filter cake was dried naturally to give Z1-a (5.5 g), yield: 50.50%. MS m / z (ESI): 364 [M+H]+, 366 [M+H]+. Step 2: Z1-a (300 mg, 823.8 umol) and ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (455 mg, 1.65 mmol) were mixed and added to an aqueous 1,4-dioxane solution (5 mL, 20%). Then K2CO3 (342 mg, 2.41 mmol) and catalyst Pd(dppf)Cl2 (13.1 mg, 0.1 mmol) were added. Under a nitrogen atmosphere, the mixture was heated to 100°C and stirred for 12 hours. After the reaction was complete, the reaction mixture was purified by column chromatography (PE / EA = 15% to 100%) to give Z1-b (200 mg), yield: 56.10%. MS m / z (ESI): 434 [M+H]+. Step 3: Z1-b (200 mg, 0.46 mmol) was added to a THF / H2O solution (2 mL, 50%). Then LiOH (40 mg) was added, and the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the pH was adjusted to neutrality with dilute hydrochloric acid (2 mol / L), followed by purification by column chromatography (DCM / MeOH = 0% to 10%) to give intermediate Z1 (160 mg), yield: 86.9%. MS m / z (ESI): 406 [M+H]+. Preparation of Intermediate Z2 Referring to the method in Preparation of Intermediate Z1, ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate     was     replaced     with     methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate to prepare Intermediate Z2, MS m / z (ESI): 401 [M+H]+. Preparation of Intermediate Z3 Step 1: Ethyl 4-hydrazinyl-2-(methylthio)pyrimidine-5-carboxylate (2.5 g, 10.96 mmol) was added to trimethyl orthoformate (5 mL). One drop of TFA was added, and the mixture was then heated to reflux and stirred for 2 hours. After the reaction was complete, the mixture was concentrated to give Z3-a (2.2 g), yield: 84.3%. MS m / z (ESI): 239 [M+H]+. Step 2: Z3-a (2.2 g, 9.24 mmol) and (5-fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (2.2 g) were added to a microwave tube. The reaction was carried out under microwave irradiation at 60°C for 30 min. DCM was added, and after uniform dispersion by sonication, the mixture was filtered to give Z3-b (1 g), yield: 30.3%. MS m / z (ESI): 358 [M+H]+. Step 3: Z3-b (1 g, 2.8 mmol) was added to an aqueous tetrahydrofuran solution (5 mL, 50%). Then LiOH (150 mg) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was complete, a hydrochloric acid solution (2 mol / L) was added to adjust the pH to neutrality, followed by purification by column chromatography (DCM / MeOH = 2% to 10%) to give Z3 (500 mg), yield: 54.2%. MS m / z (ESI): 330 [M+H]+. Preparation of Intermediate Z4 Step 1: 6-Amino-5-bromopyrimidin-2(1H)-one (50 g, 263.16 mmol) and ethyl 3-bromopyruvate (128.30 g, 657.90 mmol) were dissolved in AcOH (500 mL). The reaction mixture was stirred at 120°C for 3 h. After the reaction was complete, the mixture was cooled to room temperature, concentrated to remove most of the acetic acid, and added with water. The resultant was extracted with ethyl acetate four times. The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by CombiFlash (120 g, 0% to 10% MeOH / DCM) to give Z4-a (13 g, yellow solid), yield: 17.27%. MS m / z (ESI): 286.0 [M+H]+. Step 2: Z4-a (13 g, 45.44 mmol) was dissolved in MeOH (130 mL), and then an aqueous NaOH solution (6.36 g, 159.05 mmol, 50 mL) was added thereto. The reaction mixture was stirred at 50°C for 4 hours. After the reaction was complete, the resultant was cooled to room temperature, and concentrated to remove MeOH. The aqueous phase was cooled to 0°C, and adjusted to pH=2-3 with dilute hydrochloric acid (2 mol / L). A solid precipitated, which was filtered. The filter cake was washed three times with water and dried under vacuum to give Z4-b (4.8 g, brown solid, crude), yield: 40.94%. MS m / z (ESI): 258.0 [M+H]+. Step 3: DMF (67.99 mg, 930.13 gmol, 72.02 gL) was added to a suspension of Z4-b (4.8 g, 18.60 mmol) in SOCl2 (65.52 g, 550.73 mmol, 40 mL). The mixture was stirred at 80°C for 2 h. The reaction mixture was then concentrated, dissolved in DCM (29.93 mL), and aqueous ammonia (13.04 g, 372.05 mmol) was added dropwise to the resulting mixture at 0°C. The mixture was then stirred at 25°C for 1 h. After the reaction was complete, the mixture was filtered, and the filter cake was washed with MeOH. The filter cake was dried under vacuum to give Z4-c (3.5 g, brown solid), yield: 73.20%. MS m / z (ESI): 257.0 [M+H]+. Step 4: Z4-c (3.5 g, 13.62 mmol) was dissolved in POCl3 (67.85 g, 442.53 mmol, 40 mL), and then DIPEA (8.80 g, 68.08 mmol, 11.86 mL) was added dropwise thereto. The reaction mixture was stirred at 120°C for 14 h. After the reaction was complete, the mixture was cooled to room temperature, concentrated, and purified by CombiFlash (80 g, 0% to 25% EA / PE) to give Z4-d (1.2 g, light yellow solid), yield: 34.23%. MS m / z (ESI): 256.9 [M+H]+. Step 5: Z4-d (1.2 g, 4.66 mmol) and (5-fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (935.00 mg, 5.59 mmol) were dissolved in DCM (15 mL), and then DIPEA (1.20 g, 9.32 mmol, 1.62 mL) was added. The reaction mixture was stirred at room temperature for 1 h. After the reaction was complete, the reaction mixture was concentrated and purified by CombiFlash (24 g, 0% to 100% EA / PE) to give Z4-e (1.78 g, light yellow solid), yield: 98.38%. MS m / z (ESI): 388.0 [M+H]+. Step 6: Z4-e (300 mg, 772.81 pmol) and 4-formylphenylboronic acid pinacol ester (269.03 mg, 1.16 mmol) were dissolved in a mixture of water (1.5 mL) / 1,4-dioxane (7.5 mL). Then Pd(dppf)Cl2 (56.55 mg, 77.28 pmol) and NaHCO3 (324.61 mg, 3.86 mmol) were added. The reaction mixture was stirred at 100°C for 1.5 h. After the reaction was complete, the reaction mixture was filtered. The filtrate was concentrated and purified by CombiFlash (12 g, 0% to 5% MeOH / DCM) to give Intermediate Z4 (201 mg, light yellow solid), yield: 62.91%. MS m / z (ESI): 414.1 [M+H]+. Preparation of Intermediate Z5 Step 1: Under nitrogen protection, NaH (1.67 g, 41.75 mmol) was dissolved in DMSO (16 mL). The temperature was then lowered to 0°C, and a solution (16 mL) of ethyl diphenylmethyleneglycinate (6.14 g, 22.96 mmol) in DMSO was added. The mixture was stirred at 0°C for 5 minutes, and the reaction mixture turned orange-yellow. 2-Methylthio-4-chloro-5-bromopyrimidine (5 g, 20.88 mmol) was dissolved in DMSO (16 mL) and added dropwise to the above reaction mixture at 0°C. The reaction mixture was then slowly warmed to 25°C and stirred under nitrogen protection for 2 h, and the reaction mixture turned dark red. After the reaction was complete, the reaction mixture was quenched with saturated ammonium chloride. The aqueous phase was extracted with ethyl acetate (100 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (EA / PE=9% to 11%) to give Z5-a (9.8 g, yellow oil), yield: 99.80%. MS m / z (ESI): 470.2, 472.2 [M+H]+. Step 2: Z5-a (5 g, 10.63 mmol) was dissolved in a mixed solution of THF (50 mL) / water (30 mL). After the solution was cooled to 0°C, concentrated hydrochloric acid (10 mL, 120.00 mmol) was slowly added. The reaction mixture was stirred at 0°C for 10 minutes, then slowly warmed to 25°C and reacted for another 1 hour. After the reaction was complete, the pH of the reaction mixture was adjusted to 8 to 9 with aqueous NaOH solution (20 wt%). The aqueous phase was then extracted with ethyl acetate (30 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (EA / PE=50% to 55%) to give Z5-b (3.2 g, yellow oil), yield: 98.32%. MS m / z (ESI): 306.0, 308.0 [M+H]+. Step 3: Formic acid (6 mL, 159.06 mmol) and acetic anhydride (6 mL, 64.06 mmol) were mixed and the reaction mixture was stirred at 50°C for 1 hour. The reaction mixture was then cooled to 25°C. Z5-b (3.2 g, 10.45 mmol) was dissolved in DCM (30 mL), and then the above reaction mixture was added and stirred at 25°C for 2 h. After the reaction was complete, the pH of the reaction mixture was adjusted to 8 to 9 with aqueous NaOH solution (20 wt%). The aqueous phase was then extracted with DCM (100 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (EA / PE=55% to 60%) to give Z5-c (3.25 g, white solid), yield: 93.05%. MS m / z (ESI): 334.0 [M+H]+, 336.0 [M+H]+. Step 4: Z5-c (3.2 g, 9.58 mmol) was dissolved in 1,4-dioxane (50 mL), POCl3 (2.67 mL, 28.73 mmol) was added, and the reaction mixture was stirred at 110°C for 1 h. After the reaction was complete, the reaction mixture was concentrated, and adjusted to pH=8-9 with saturated sodium bicarbonate solution. The aqueous phase was extracted with ethyl acetate (100 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (EA / PE=55% to 60%) to give Z5-d (3 g, light yellow solid), yield: 99.09%. MS m / z (ESI): 316.0 [M+H]+, 318.0 [M+H]+. Step 5: At room temperature, Z5-d (1 g, 3.16 mmol) was dissolved in DCM (15 mL). mCPBA (2.18 g, 12.64 mmol) was then added, and the reaction mixture was stirred at 25°C for 3 h. After the reaction was complete, the reaction mixture was concentrated and purified by column chromatography (PE / EA=40% to 50%) to give Z5-e (900 mg, yellow solid), yield: 81.73%. MS m / z (ESI): 348.0 [M+H]+, 350.0 [M+H]+. Step 6: At room temperature, (5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methanamine (247.77 mg, 1.48 mmol) and Z5-e (430 mg, 1.24 mmol) were dissolved in DCM (10 mL), and stirred in an ice bath for 15 minutes. Then, triethylamine (342.39 pL, 2.47 mmol) was added, and the reaction mixture was stirred at 25°C for 2 h. After the reaction was complete, the reaction mixture was concentrated and purified by column chromatography (PE / EA=40% to 50%) to give Z5-f (300 mg, yellow solid), yield: 55.81%. MS m / z (ESI): 434.8 [M+H]+, 436.8 [M+H]+. Step 7: Z5-f (60 mg, 0.14 mmol) was dissolved in a mixed solution of MeOH (1 mL) / THF (1 mL). 10% wet palladium on carbon (14.67 mg, 0.01 mmol) was then added, and the reaction mixture was stirred at 25°C for 4 h. After the reaction was complete, the mixture was filtered, the filter cake was washed with MeOH (10 mL) and EA (10 mL), and the filtrates were combined and concentrated to give Z5-g (40 mg, white solid, crude), yield: 81.43%. MS m / z (ESI): 356.9 [M+H]+. Step 8: Z5-g (40 mg, 0.11 mmol) was dissolved in a mixed solution of MeOH (1 mL), water (1 mL), and THF (1 mL), and then LiOH (23.07 mg, 0.55 mmol) was added. The reaction mixture was stirred at 60°C for 18 h. After the reaction was complete, the pH of the reaction mixture was adjusted to 3 to 4 with hydrochloric acid (2 mol / L). The aqueous phase was then extracted with ethyl acetate (20 mLx2), and the combined organic phases were concentrated to give Intermediate Z5 (30 mg, white solid), yield: 81.41%. MS m / z (ESI): 329.0 [M+H]+. Preparation of Intermediate Z6 Step 1:   Under nitrogen protection, Z5-f (200 mg, 0.46 mmol) and 6-cyclopropylpyridine-3-boronic acid pinacol ester (168.96 mg, 0.69 mmol) were dissolved in a mixed solution of 1,4-dioxane (3 mL) and water (1 mL). K2CO3 (190.51 mg, 1.38 mmol) and Pd(dppf)Cl2 (34.09 mg, 0.05 mmol) were then added, and the reaction mixture was stirred at 100°C for 2 h under nitrogen protection. After the reaction was complete, the reaction mixture was poured into water (10 mL), and the aqueous phase was extracted with ethyl acetate (100 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (EA / PE=50% to 80%) to give Z6-a (200 mg, white solid), yield: 91.92%. MS m / z (ESI): 474.2 [M+H]+. Step 2: Z6-a (200 mg, 0.42 mmol) was dissolved in a mixed solution of THF (3 mL) / methanol (1 mL) / water (1 mL). LiOH (88.61 mg, 2.11 mmol) was then added, and the temperature was raised to 60°C and the reaction mixture was stirred for 18 h. After the reaction was complete, the reaction mixture was concentrated to give Intermediate Z6 (180 mg, white solid, crude), yield: 95.67%. MS m / z (ESI): 445.9 [M+H]+. Preparation of Intermediate Z7 Z7 Step 1:    Compound 8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4] triazolo[4,3-c]pyrimidin-5-amine (300 mg, 823.8 pmol) and compound ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (462 mg, 1.65 mmol) were mixed and added to an aqueous dioxane solution (5 mL, v / v = 20%). K2CO3 (342 mg, 2.47 mmol) and Pd(dppf)Cl2 (73.1 mg, 0.1 mmol) were added, and the mixture was heated to 100°C under nitrogen protection and stirred for 12 hours. After the reaction was complete, the reaction mixture was purified by column chromatography (15% to 100% PE / EA) to give Z7-a (200 mg), yield: 56.10%. MS m / z (ESI): 438 [M+H]+. Step 2: Z7-a (200 mg, 0.46 mmol) was added to MeOH, and 10% palladium on carbon (20 mg) was added. The mixture was heated to 40°C under hydrogen protection and stirred for 5 hours. After the reaction was complete, the resultant was filtered, and the filtrate was concentrated to give Z7-b (200 mg), yield: 100%. MS m / z (ESI): 440 [M+H]+. Step 3: Z7-b (200 mg, 0.46 mmol) was added to a THF / H2O solution (2 mL, v / v = 50%). Lithium hydroxide (40 mg) was then added, and the mixture was stirred at room temperature for 3 hours. After the reaction was complete, an aqueous hydrochloric acid solution (2 mol / L) was added to adjust the pH to neutrality, and the mixture was purified by column chromatography (0% to 10% DCM / MeOH) to give Intermediate Z7 (150 mg), yield: 79.3%. MS m / z (ESI): 412 [M+H]+. Preparation of Intermediate Z8 Step 1: To a solution of 8-bromo-5-(methylthio)imidazo[1,5-c]pyrimidine (1 g, 4.10 mmol) in DCM (20 mL) was added m-chloroperoxybenzoic acid (1.08 g, 5.33 mmol), and the mixture was stirred at 0°C under a nitrogen atmosphere for 5 hours. Then, at 0°C, triethylamine (2.84 mL, 20.5 mmol) and (5-fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (0.68 g, 4.10 mmol) were added to the mixture, and the mixture was stirred at 25°C under a nitrogen atmosphere for 18 hours. After the reaction was complete, the mixture was concentrated and purified by silica gel chromatography (DCM:MeOH = 100:1 to 40:1) to give Z8-a (1 g, yellow solid), yield: 67.1%. MS m / z (ESI): 365.0 [M+H]+. Step 2: To a solution of Z8-a (500 mg, 1.38 mmol) in 1,4-dioxane (20 mL) and water (4 mL) were added ethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate (763 mg, 2.75 mmol), K2CO3 (380 mg, 2.75 mmol), and Pd(PPh3)4 (318 mg, 0.28 mmol), and the mixture was stirred at 90°C under a nitrogen atmosphere for 7 hours. After the reaction was complete, the reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (30 mL*3). The combined organic phases were washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (DCM:MeOH = 100:1 to 20:1) to give Z8-b (260 mg, yellow solid), yield: 43.6%. MS m / z (ESI): 434.1 [M+H]+. Step 3: At 0°C under a nitrogen atmosphere, NIS (141 mg, 0.63 mmol) was slowly added to a solution of Z8-b (160 mg, 0.37 mmol) in DMF (6 mL), and the reaction mixture was stirred at 25°C under a nitrogen atmosphere for 2 hours. After the reaction was complete, the reaction mixture was poured into ice water (20 mL) and extracted with ethyl acetate (30 mL*3). The combined organic phases were washed with saturated brine (10 mL*3), dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (DCM:MeOH = 500:1 to 40:1) to give Z8-c (88 mg, red solid), yield: 42.6%. MS m / z (ESI): 559.8 [M+H]+. Step 4: To a solution of Z8-c (59 mg, 0.11 mmol) in DMSO (2.5 mL) were added sodium methanesulfinate (32 mg, 0.32 mmol) and CuI (60 mg, 0.32 mmol). Under a nitrogen atmosphere, the mixture was heated under microwave irradiation at 120°C for 20 min and then reacted under microwave at 100°C for 3 hours. After the reaction was complete, the reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (30 mLx3). The combined organic phases were washed with saturated brine (10 mLx3), dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (DCM:MeOH = 100:1 to 30:1) to give Z8-d (50 mg, yellow solid), yield: 92.7%. MS m / z (ESI): 511.9 [M+H]+. Step 5: To a solution of Z8-d (40 mg, 0.08 mmol) in methanol (4 mL) and water (0.4 mL) was added lithium hydroxide monohydrate (40 mg, 0.95 mmol), and the mixture was stirred at 25°C for 5 h. After the reaction was complete, the mixture was concentrated and diluted with water (5 mL). The pH was adjusted to 7 with aqueous hydrochloric acid solution (2 mol / L). The resultant was extracted with ethyl acetate (30 mLx3), and the combined organic phases were dried over anhydrous sodium sulfate and concentrated to give Intermediate Z8 (35 mg, yellow solid), yield: 92.5%. MS m / z (ESI): 483.9 [M+H]+. Preparation of Intermediate Z9 Z10-a                               Z9 Step 1: To a single-neck flask were added Z10-a (80.0 mg, 0.180 mmol), methanol (5 mL), and water (0.5 mL) at room temperature. Lithium hydroxide monohydrate (80.0 mg, 1.91 mmol) was added with stirring, and the reaction was carried out at 25°C for 3 hours. After the reaction was complete, the reaction mixture was poured into water (20 mL), and filtered. The filter cake was washed with water (5 mL). The filter cake was dried to give Intermediate Z9 (68 mg, light yellow solid), yield: 90.88%. MS m / z (ESI): 406.2 [M+H]+. Preparation of Intermediate Z10 Step 1: 8-Bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (400 mg, 1.10 mmol) and methyl 5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)picolinate (580 mg, 2.20 mmol) were dissolved in 1,4-dioxane (15 mL) and water (2 mL). Pd(PPh3)4 (255 mg, 0.22 mmol) and K2CO3 (304.43 mg, 2.20 mmol) were added, and the mixture was stirred at 90°C under argon protection for 20 hours. After the reaction was complete, the reaction mixture was poured into water, and extracted with ethyl acetate (30 mLx2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by CombiFlash (PE / EA = 0% to 90%) to give Z10-a (78 mg, yellow solid), yield: 16.89%. MS m / z (ESI): 420.1 [M+H]+. Step 2: Z10-a (78 mg, 0.19 mmol) was dissolved in DMF (5 mL), and cooled to 0°C. NIS (42 mg, 0.19 mmol) was added, and the mixture was stirred at room temperature for 6s. After the reaction was complete, the reaction mixture was poured into water, and extracted with ethyl acetate (30 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and then purified by CombiFlash (PE / EA = 0% to 100%) to give Z10-b (70 mg, yellow solid), yield: 69%. MS m / z (ESI): 546.0 [M+H]+. Step 3: Z10-b (50 mg, 0.092 mmol) was dissolved in methanol (12 mL) and water (3 mL), and lithium hydroxide monohydrate (39 mg, 0.92 mmol) was added. The mixture was stirred at room temperature for 20 hours, adjusted to pH=5 with dilute hydrochloric acid (1 mol / L), and extracted with dichloromethane (30 mL*3). The combined organic phases were dried over anhydrous sodium sulfate and concentrated to give Intermediate Z10 (35 mg, yellow solid, crude), yield: 71.8%. MS m / z (ESI): 532.0 [M+H]+. Preparation of Intermediate Z11 Step 1: Z8-a (1 g, 2.75 mmol), di-tert-butyl dicarbonate (1.20 g, 5.51 mmol), triethylamine (0.83 g, 8.25 mmol) and 4-dimethylaminopyridine (0.34 g, 2.75 mmol) were dissolved in anhydrous DCM (20 mL), and the mixture was stirred at 35°C under nitrogen protection for 2 hours. After the reaction was complete, the reaction mixture was poured into water, and extracted twice with dichloromethane. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (PE:EA = 5:1) to give Z11-a (1.13 g, light yellow solid), yield: 88.6%. MS m / z (ESI): 463.2 [M+H]+. Step 2: Z11-a (460 mg, 0.99 mmol), tert-butyl piperazine-1-carboxylate (50.90 mg, 0.32 mmol), cesium carbonate (970.48 mg, 2.98 mmol), Xantphos (229.80 mg, 0.40 mmol) and Pd2(dba)3 (181.83 mg, 0.20 mmol) were dissolved in 1,4-dioxane (5 mL). The mixture was purged with nitrogen three times, heated to 90°C, and stirred at 90°C for 18 hours. After the reaction was complete, the reaction mixture was poured into water, and extracted twice with dichloromethane. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (PE:EA = 3:1) to give Z11-b (440 mg, light yellow solid), yield: 77.9%. MS m / z (ESI): 569.5 [M+H]+. Step 3: Z11-b (200 mg, 0.35 mmol) was dissolved in DMF (8 mL), and cooled to 0°C. NIS (134.52 mg, 0.60 mmol) was then added, and the mixture was slowly warmed to 25°C and stirred for 18 hours. After the reaction was complete, the reaction mixture was poured into water, and extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (PE:EA = 2:1) to give Z11-c (50 mg, light yellow solid), yield: 20.47%. MS m / z (ESI): 695.6 [M+H]+. 'H NMR (400 MHz, CDCh) 8 7.77 (s, 1H), 6.90 (s, 1H), 6.64 - 6.53 (m, 1H), 6.48 (dd, J = 8.7, 4.0 Hz, 1H), 4.92 (s, 2H), 4.47 (t, J = 8.7 Hz, 2H), 3.60-3.72 (m, 4H), 3.15-3.25 (m, 2H), 2.90-2.99 (m, 4H), 1.42 (s, 9H), 1.28 (s, 9H). Step 4: Z11-c (25 mg, 0.05 mmol) was dissolved in DMSO (2 mL). CuI (17.14 mg, 0.09 mmol) and sodium methanesulfinate (8.82 mg, 0.09 mmol) were then added. The mixture was reacted under microwave at 120°C for 20 minutes, and then reacted under microwave at 100°C for 3 hours. After the reaction was complete, the reaction mixture was poured into water, extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give Z11-d (18 mg, light yellow solid, crude), which was used in the next step without further purification. MS m / z (ESI): 647.3 [M+H]+. Step 5: Z11-d (50 mg, 0.08 mmol) was dissolved in ethyl acetate (2 mL). A solution of hydrogen chloride in ethyl acetate (4 mol / L, 2 mL) was added, and the mixture was stirred at 25°C for 18 hours. After the reaction was complete, the mixture was filtered, and the filter cake was washed twice with ethyl acetate. The filter cake was dried to give Intermediate Z11 (36 mg, white solid), yield: 96.4%. MS m / z (ESI): 447.2 [M+H]+. Preparation of Intermediate Z12 Z12-b                     Z12 Step 1: 3-Bromo-6-chloro-2-fluoropyridine (8.8 g, 41.82 mmol) was dissolved in ethanol (40 mL). Hydrazine hydrate (2.96 g, 50.18 mmol, 85% purity) was added, and the mixture was heated to 80°C and stirred at 80°C overnight. After the reaction was complete, the reaction mixture was concentrated to give Z12-a (9.3 g), yield: 99.96%. It was used directly in the next reaction. MS m / z (ESI): 221.9 [M+H]+. Step 2: Z12-a (9.3 g, 41.80 mmol) was dissolved in trimethyl orthoformate (90 mL), and the mixture was stirred at 100°C under argon protection for 4 hours. After the reaction was complete, the reaction mixture was filtered, and the filter cake was dried to give Z12-b (8.5 g), yield: 87.47%. MS m / z (ESI): 231.9 [M+H]+. Step 3: Z12-b (2 g, 8.60 mmol), (5-fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (3.31 g, 19.79 mmol) and ethanol (1 mL) were mixed and stirred at 85°C for 20 hours. After the reaction was complete, the reaction mixture was concentrated and purified by CombiFlash (0% to 10% MeOH / DCM) to give Intermediate Z12 (1.2 g, yellow solid), yield: 38.40%. MS m / z (ESI): 365.0 [M+2H]2+. Preparation of Intermediate Z13 Step 1: To 8-bromo-5-(((5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl)amino)imidazo[4,3-f]pyrimidine (100 mg, 0.28 mmol) in dimethoxyethane (2 mL) and water (0.2 mL) were added methyl 5-bromo-6-methylpyridine-2-carboxylate (126 mg, 0.55 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (174 mg, 0.69 mmol), n-butyldi(1-adamantyl)phosphine (39 mg, 0.11 mmol), K2CO3 (152 mg, 1.10 mmol) and Pd(OAc)2 (12 mg, 0.06 mmol). The mixture was stirred at 70°C under a nitrogen atmosphere for 18 hours. The reaction mixture was concentrated and purified by silica gel chromatography (eluent: DCM:MeOH = 100:1 to 20:1) to give Z13-a (45 mg, black solid), yield: 37.1%. MS m / z (ESI): 434.1 [M+H]+. Step 2: At 0°C under a nitrogen atmosphere, NIS (22 mg, 0.10 mmol) was added to a solution of Z13-a (25 mg, 0.06 mmol) in DMF (1.5 mL). The mixture was stirred at 0°C under a nitrogen atmosphere for 30 minutes. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (30 mLz3). The combined organic phases were washed with brine (10 mL), dried over anhydrous sodium sulfate, and concentrated to give Z13-b (20 mg, yellow liquid, crude), yield: 43.3%. MS m / z (ESI): 560.1 [M+H]+. Step 3: To Z13-b (20 mg, 0.03 mmol) in methanol (1 mL) and water (0.2 mL) was added lithium hydroxide monohydrate (10 mg, 0.43 mmol). The reaction mixture was stirred at 25°C for 2 hours. The reaction mixture was concentrated to give Intermediate Z13 (22 mg, yellow solid), yield: 96.7%. MS m / z (ESI): 546.0 [M+H]+. Preparation of Intermediate Z15 Z10-a                          Z15-a                                Z15 Step 1: Z10-a (190 mg, 453.02 pmol) was dissolved in DCM (50 mL). The temperature was lowered to 0°C under argon protection. NBS (80.63 mg, 453.02 gmol) was added, and the mixture was stirred at 0°C for 1 hour. After the reaction was complete, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (MeOH:DCM = 0% to 10%) to give Z15-a (45 mg, 90.31 gmol, yellow solid), yield: 19.93%. MS m / z (ESI): 498 [M+H]+. Step 2: Z15-a (45 mg, 90.31 umol) was dissolved in MeOH (5 mL). A solution of NaOH (3.61 mg, 90.31 pmol) in methanol / water (5 mL / 0.5 mL) was added with stirring at room temperature, and the mixture was stirred at room temperature for 3 hours. After the reaction was complete, the pH of the reaction mixture was adjusted to 4-5 with concentrated hydrochloric acid in an ice bath. The mixture was concentrated to give Intermediate Z15 (43.73 mg, yellow solid, crude), yield: 100.00%. MS m / z (ESI): 484 [M+H]+. Preparation of Intermediate Z16 Step 1: Intermediate Z9 (170 mg, 419.36 gmol) was dissolved in DMF (10 mL). Under ice bath, NCS (56.00 mg, 419.36 pmol) was slowly added portionwise. After the reaction was complete, water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The combined organic phases were washed twice with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give Intermediate Z16 (150 mg, yellow solid), yield: 81.3%. MS m / z (ESI): 440.1 [M+H]+. Preparation of Intermediate Z17 Z10-a                                Z17-a                                  Z17 Step 1: Z10-a (323 mg, 0.77 mmol) was dissolved in super dry DCM (15 mL), and selectfluor (409 mg, 1.16 mmol) was added. The mixture was stirred at room temperature for 20 hours. After the reaction was complete, the reaction mixture was poured into water, and extracted with dichloromethane (30 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by CombiFlash (0% to 10% MeOH / DCM) to give Z17-a (35 mg, yellow solid), yield: 10.39%. MS m / z (ESI): 438.1 [M+H]+. Step 2: Z17-a (35 mg, 0.08 mmol) was dissolved in a mixed solution of MeOH / water (6 mL / 1 mL). Lithium hydroxide monohydrate (20 mg, 0.48 mmol) was added, and the reaction mixture was stirred at room temperature for 20 hours. After the reaction was complete, the reaction mixture was neutralized to pH=5 with HCl solution (6 mol / L) and concentrated to give Intermediate Z17 (33 mg, crude), yield: 97.41%. MS m / z (ESI): 424.1 [M+H]+. Preparation of Intermediate Z18 Referring to the preparation method of Intermediate Z6, Z5-f was replaced with 8-bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5- amine to prepare Intermediate Z18, MS m / z (ESI): 439.1 [M+H]+. Preparation of Intermediate Z19 Z19-a Z19 Step 1:    8-Bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c] pyrimidin-5-amine (0.9 g, 2.26 mmol) and methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-carboxylate (896.60 mg, 3.40 mmol) were dissolved in 1,4-dioxane (20 mL) and water (2 mL). Ruphos-Pd-G3 (379.06 mg, 452.68 pmol) and K3PO4 (672.63 mg, 3.17 mmol) were added, and the reaction mixture was stirred at 100°C under argon protection for 20 hours. After the reaction was complete, the reaction mixture was poured into water, and extracted with DCM. The combined organic phases were dried over anhydrous sodium sulfate, concentrated, and purified by CombiFlash (0% to 100% EA / PE) to give Z19-a (415 mg, yellow solid), yield: 40.31%. MS m / z (ESI): 455.1 [M+H]+. Step 2: Z19-a (415 mg, 912.41 pmol) was dissolved in THF (8.81 mL), and cooled to -78°C. DIBAL-H (1 mol / L, 3.01 mL) was added, and the reaction mixture was stirred at -78°C for 1 hour. After the reaction was complete, the reaction mixture was quenched with saturated aqueous NH4Cl solution, and filtered. The filtrate was extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated to give Intermediate Z19 (360 mg, crude), yield: 92.88%. MS m / z (ESI): 425.1 [M+H]+. Preparation of Intermediate Z20 Z20 Step 1:   8-Bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin- 5-amine  (1 g,  2.75  mmol) was dissolved in water (4 mL) and 1,4-dioxane. [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (302.20 mg, 413.01 pmol), potassium carbonate  (761.08  mg,  5.51 mmol),  and tert-butyl  4-(6-methyl-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridin-2-yl)piperidine-1-carboxylate (1.33 g, 3.30 mmol) were added. The reaction was carried out at 90°C for 16 h. LCMS showed the reaction was complete. The reaction mixture was filtered and concentrated to dryness under reduced pressure. The residue was purified by combiflash with PE:EA = 1:2 to give compound Z20-1 (1.11 g, 1.99 mmol, 72.16% yield) as a yellow solid. MS m / z (ESI): 559.3 [M+H]+. Step 2: Compound Z20-1 (200 mg, 358.01 pmol) was dissolved in DMF (2 mL). Under ice bath conditions, N-iodosuccinimide (80.54 mg, 358.01 umol) was added, and the mixture was stirred at room temperature for 15 minutes. LC-MS showed the reaction was complete. The reaction mixture was concentrated to dryness under reduced pressure, and purified by silica gel column chromatography (EA:PE = 0% to 100%) to give compound Z20-2 (180 mg, 262.95 pmol, 73.45% yield) as a yellow solid. MS m / z (ESI): 685.1 [M+H]+. Step 3: Compound Z20-2 (200 mg, 292.17 pmol) was dissolved in DMSO (4 mL). Under argon protection, sodium bisulfite (89.40 mg, 876.50 pmol) and copper monoiodide (166.93 mg, 876.50 pmol) were added. The temperature was raised to 100°C, and the mixture was stirred for 1 hour. LCMS showed the reaction was complete. The reaction mixture was filtered and concentrated to dryness under reduced pressure. The residue was purified by combi-flash with DCM:MeOH = 10:1 to give compound Z20-3 (150 mg, 235.58 pmol, 80.63% yield) as a yellow solid. MS m / z (ESI): 637.3 [M+H]+. Step 4: Compound Z20-3 (150 mg, 235.58 pmol) was dissolved in trifluoroacetic acid (1 mL) in dichloromethane (5 mL). The reaction was carried out at room temperature for 1 h. LCMS showed the reaction was complete. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by combiflash with DCM:MeOH = 10:1 to give compound Z20 (110 mg, 204.99 pmol, 87.1% yield) as a yellow solid. MS m / z (ESI): 537.2 [M+H]+. Preparation of Intermediate Z21 Step 1:    5-Bromo-2-iodopyrimidine (5 g, 17.55 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (5.97 g, 19.31 mmol) were dissolved in water (15 mL) and 1,4-dioxane (100 mL). Under argon protection, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.92 g, 2.63 mmol) and potassium carbonate (7.28 g, 52.65 mmol) were added. The temperature was raised to 80°C and stirred for 16 hours. LCMS showed the reaction was complete. The reaction mixture was filtered and concentrated to dryness under reduced pressure. The residue was purified by combiflash with PE:EA = 2:1 to give tert-butyl 4-(5-bromopyrimidin-2-yl)-3,6-dihydropyridine-1(2H)- carboxylate (5 g, 14.70 mmol, 83.74% yield) as a yellow solid. MS m / z (ESI): 342.1 [M+H]+. Step 2: tert-Butyl 4-(5-bromopyrimidin-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (1 g, 2.94 mmol) and bis(pinacolato)diboron (1.12 g, 4.41 mmol) were dissolved in 1,4-dioxane (20 mL). [1,1'-Bis(diphenylphosphino)ferrocene] dichloropalladium (II) (322.30 mg, 440.90 pmol) and potassium acetate (865.39 mg, 8.82 mmol) were added. The mixture was purged with argon three times, heated to 95°C, and stirred overnight. LCMS showed product formation. The solid was filtered off, and the mother liquor was concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (20 g, 0% to 20% EA / PE) to give tert-butyl      4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)-3,6-dihydropyridine- 1(2H)-carboxylate (800 mg, 2.07 mmol, 70.28% yield). MS m / z (ESI): 330.3 [M-56+H]+. Step 3:   Tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)-3,6- dihydropyridine-1(2H)-carboxylate (1 g, 2.58 mmol) and 8-bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (1.03 g, 2.58 mmol) were dissolved in water (3 mL) and 1,4-dioxane (20 mL). Under argon protection, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (283.40 mg, 387.32 pmol) and potassium carbonate (713.72 mg, 5.16 mmol) were added. The temperature was raised to 80°C and stirred for 16 hours. LCMS showed the reaction was complete. The reaction mixture was filtered and concentrated to dryness. The residue was purified by combiflash (PE:EA = 2:1) to give compound Z21-1 (1 g, 1.73 mmol, 67.00% yield) as a yellow solid. MS m / z (ESI): 522.2 [M-56+H]+. Step 4: Compound Z21-1 (200 mg, 346.00 pmol) was dissolved in ethyl acetate (10 mL). Pd / C (42.02 mg, 346.00 pmol) was added, and the mixture was stirred at room temperature for 2 hours under hydrogen protection. Reaction progress was monitored by LC-MS. The reaction mixture was filtered and concentrated to dryness under reduced pressure to give compound Z21-2 (190 mg, 327.56 pmol, 94.67% yield) as a colorless oil. MS m / z (ESI): 524.2 [M-56+H]+. Step 5: Compound Z21-2 (200 mg, 344.80 nmol) was dissolved in trifluoroacetic acid (3 mL) and dichloromethane (6 mL) was added. The reaction was carried out at room temperature for 2 h. LCMS showed the reaction was complete. The reaction mixture was concentrated to dryness under reduced pressure, adjusted to pH=8 with aqueous sodium bicarbonate solution, extracted twice with DCM, washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The residue was purified by combiflash with DCM:MeOH = 5:1 to give compound Z21 (75 mg, 156.27 pmol, 45.32% yield) as a light yellow solid. MS m / z (ESI): 480.2 [M+H]+. Preparation of Intermediate Z22 Z22-b                                           Z22 Step     1:     8-Bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5- c]pyrimidin-5-amine (320 mg, 804.77 umol) and Z22-a (312.50 mg, 804.77 umol) were dissolved in dioxane (10 mL), dimethyl sulfoxide (1 mL), and water (1 mL). Under argon protection, Pd(dppf)Cl2 (58.89 mg, 80.48 umol) and K2CO3 (333.67 mg, 2.41 mmol) were added. The temperature was raised to 90°C and the reaction mixture was stirred for 3 hours. Water and ethyl acetate were added, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (12 g, 0% to 40% EA / PE) to give compound Z22-b (350 mg, 604.42 pmol, 75.11% yield) as a light yellow solid. MS m / z (ESI): 579.3 [M+H]+. Step 2: Compound Z22-b (350 mg, 604.42 pmol) was dissolved in DCM (6 mL), and TFA (2 mL) was added. The mixture was stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent. The residue was then dissolved in dichloromethane, and the pH was adjusted to greater than 8 with aqueous sodium bicarbonate solution. The resultant was extracted three times with dichloromethane and methanol (10:1). The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product Z22 (240 mg, 501.10 pmol, 82.91% yield) as a light yellow solid, which was used in the next step without purification. MS m / z (ESI): 479.2 [M+H]+. Preparation of Intermediate Z23-d Z23-C Step 1: Under argon protection, 1,4-dibromobenzene (1 g, 4.24 mmol), compound Z23-a (786.44 mg, 2.54 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (310.17 mg, 423.90 pmol), potassium carbonate (1.76 g, 12.72 mmol), 1,4-dioxane (20 mL), and water (5 mL) were mixed and then heated to 85°C for reaction for 2 hours. The reaction mixture was filtered, water was added to the filtrate, and extraction was performed with ethyl acetate (20 mL*2). The combined organic layers were washed with saturated brine and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 75%:25%) to give compound Z23-b (540 mg, 1.60 mmol, yield 37.66%) as a colorless liquid. The crude product was used directly in the next step. MS m / z (ESI): 282.0 [M+H-56]+. Step 2: Under argon protection, compound Z23-b (490 mg, 1.45 mmol), bis(pinacolato)diboron (919.69 mg, 3.62 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (106.00 mg, 144.87 pmol), potassium acetate (426.53 mg, 4.35 mmol), and 1,4-dioxane (35 mL) were mixed and then heated to 90°C for reaction for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 85%:15%) to give compound Z23-c (420 mg, 1.09 mmol, yield 75.24%) as a yellow solid. MS m / z (ESI): 330.2 [M+H-56]+. Step 3: Under hydrogen atmosphere, palladium on carbon (11.05 mg, 103.81 pmol) was added to a solution of compound Z23-c (400 mg, 1.04 mmol) in methanol (10 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction mixture was filtered, and the filtrate was concentrated to dryness to give compound Z23-d (380 mg, 981.10 pmol, yield 94.51%) as a colorless oil. The crude product was used directly in the next step. MS m / z (ESI): 332.2 [M+H-56]+. Preparation of Intermediate Z24 Step 1: Tert-butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (2 g, 7.86 mmol) was dissolved in toluene (30 mL). 1,4-Dibromobenzene (5.56 g, 23.59 mmol), cesium carbonate (7.67 g, 23.59 mmol), bis(dibenzylideneacetone)palladium (719.99 mg, 786.26 pmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (908.92 mg, 1.57 mmol) were added. The reaction was carried out at 110°C overnight. LCMS monitoring showed the starting material disappeared. Water was added to the reaction mixture, which was extracted twice with ethyl acetate, washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. Purification by CombiFlash (40 g, 0% to 40% EA / PE) successfully gave compound Z24-a (1.3 g, 3.18 mmol, yield: 40.39%) as a yellow solid product. MS m / z (ESI): 409.2 [M+H]+. Step 2: Compound Z24-a (1.3 g, 3.18 mmol) was dissolved in 1,4-dioxane (15 mL). [1,1'-Bis(diphenylphosphinoferrocene]dichloropalladium (II) (464.29 mg, 635.14 pmol) and bis(pinacolato)diboron (1.61 g, 6.35 mmol) were added. The mixture was purged with argon three times and reacted at 100°C for 16 h. LCMS monitoring showed the starting material disappeared and product was formed. Water was added to the reaction mixture, which was extracted twice with ethyl acetate, washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. Purification by CombiFlash (20 g, 0% to 40% EA / PE) successfully gave compound Z24-b (1 g, 2.19 mmol, yield: 68.99%) as a yellow solid product. MS m / z (ESI): 457.3 [M+H]+. Step 3:  Compound Z24-b  (250 mg, 628.73 pmol) and 8-bromo-1-chloro-N-((5- fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine were dissolved in 1,4-dioxane (10 mL). [1,1'-Bis(diphenylphosphinoferrocene]dichloropalladium (II) (68.94 mg, 94.31 pmol) and potassium carbonate (260.68 mg, 1.89 mmol) were added. The mixture was purged with argon three times and reacted at 100°C for 16 h. LCMS monitoring showed the starting material disappeared and product was formed. The reaction mixture was filtered and concentrated to dryness under reduced pressure. The residue was purified by CombiFlash (12 g, 0% to 25% EA / PE) to successfully give compound Z24-c (400 mg, 618.07 pmol, yield: 98.30%) as a yellow solid product. MS m / z (ESI): 647.1 [M+H]+. Step 4: Compound Z24-c (300 mg, 463.55 pmol) was dissolved in DCM (5 mL), and trifluoroacetic acid (2 mL) was added. The reaction was carried out at room temperature overnight. LCMS monitoring showed product was formed and starting material disappeared. The reaction mixture was concentrated to dryness under reduced pressure. The residue was dissolved in TEA and DCM until clear, which was then stirred for sample loading. Purification by CombiFlash (12 g, 0% to 50% MeOH / DCM) successfully gave compound Z24 (250 mg, 456.98 pmol, yield: 98.58%) as a yellow solid product. MS m / z (ESI): 547.3 [M+H]+. Preparation of Intermediate Z25 Step       1:       Compound       8-bromo-1-chloro-N-[(5-fluoro-2,3-dihydrobenzofuran-4- yl)methyl]imidazo[1,5-c]pyrimidin-5-amine (200 mg, 502.98 pmol) and tert-butyl 4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidine-1-carboxylate (194.81 mg, 502.98 pmol) were dissolved in dioxane (5 mL) and water (0.5 mL). Under argon protection, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (73.61 mg, 100.60 pmol) and potassium carbonate (139.03 mg, 1.01 mmol) were added sequentially. The temperature was raised to 95°C and the mixture was stirred for 16 hours. The reaction mixture was concentrated to dryness under reduced pressure, and purified by silica gel column chromatography (DCM:EA = 0-80%) to give Z25-a (200 mg, 345.98 pmol, 68.78% yield) as a yellow solid. MS m / z (ESI): 578 [M+H]+. Step 2: Compound Z25-a (150 mg, 259.48 pmol) was dissolved in dichloromethane (8.53 mL) and methanol (3.41 mL). A solution of hydrogen chloride in ethyl acetate (4.0 M, 64.87 pL) was added with stirring at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated to dryness under reduced pressure to give Z25 (124.02 mg, 259.48 pmol, 100.00% yield) as a yellow solid. MS m / z (ESI): 478 [M+H]+. Preparation of Intermediate Z26 Step 1: Ethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate (554 mg, 2 mmol), 8-bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (792 mg, 2 mmol), potassium carbonate (414 mg, 3 mmol), and catalyst [1,1'-bis(diphenylphosphinoferrocene]dichloropalladium(II) (146 mg, 0.2 mmol) were added to a mixed solvent of 5 ml of 1,4-dioxane and 1 ml of water. After purging with nitrogen three times, the mixture was heated to 100°C and reacted for 5 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target product was concentrated to give compound Z26-a (467 mg, 1 mmol). Yield: 50%. MS m / z (ESI): 468 [M+H]+. Step 2: Compound Z26-a (467 mg, 1 mmol) and 100 mg of lithium hydroxide were added to a mixed solvent of 5 ml of tetrahydrofuran and 2 ml of water. After stirring at room temperature for 2 hours, 2M aqueous hydrochloric acid solution was added dropwise to adjust the pH to weakly acidic. Extraction was performed three times with ethyl acetate (20 ml*3), and the combined organic phases were concentrated to give compound Z26-b (330 mg, 0.75 mmol). Yield: 75%. MS m / z (ESI): 440 [M+H]+. Step 3: Compound Z26-b (330 mg, 0.75 mmol), 1 ml of DIEA, and HATU (285 mg, 0.75 mmol) were sequentially added to 5 ml of DMF. After stirring at room temperature for 10 minutes, tert-butyl 4-aminopiperidine-1-carboxylate (200 mg, 1 mmol) was added, and the reaction was allowed to proceed for 1 hour. Silica gel was added to the resulting mixture solution which was stirred for sample loading. Column chromatography was performed using PE / EA (10% to 100%) to give Z26-c (156 mg, 0.25 mmol). Yield: 33%. MS m / z (ESI): 622 [M+H]+. Step 4: Compound Z26-c (156 mg, 0.25 mmol) was added to a mixed solution of 5 ml of dichloromethane and 1 ml of TFA, stirred at room temperature for 1 hour, and then concentrated and dried under oil pump vacuum to give compound Z26 (120 mg, 0.23 mmol). Yield: 92%. MS m / z (ESI): 522 [M+H]+. Preparation of Intermediate Z27 Step    1:    Compound    8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)[1,2,4] triazolo[4,3-c]pyrimidin-5-amine (1090 mg, 3 mmol) was added to 3 ml of pyridine. Then, 100 mg of DMAP and di-tert-butyl dicarbonate (1090 mg, 5 mmol) were added. The reaction mixture was stirred at room temperature for 5 hours. After the reaction was complete, silica gel was added, and the mixture was stirred for sample loading. Column chromatography was performed using PE / EA (25% to 100%) to give Z27-a (926 mg, 2 mmol). Yield: 66%. MS m / z (ESI): 464 [M+H]+. Step     2:     Compound     Z27-a     (926     mg,     2     mmol),     tert-butyl (1R,5S)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate (500 mg, 2.36 mmol), 100 mg of Xantphos, 100 mg of Pd2(dba)3, and cesium carbonate were sequentially added to 10 ml of 1,4-dioxane. After purging with nitrogen three times, the mixture was heated to 110°C and stirred for 10 hours. After the reaction was complete, silica gel was added, and the mixture was stirred for sample loading. Column chromatography was performed using PE / EA (10% to 100%) to give compound Z27-b (595 mg, 1 mmol). Yield: 50%. MS m / z (ESI): 596 [M+H]+. Step 3: Compound Z27-b (595 mg, 1 mmol) was added to 5 ml of dichloromethane. Then, 2 ml of trifluoroacetic acid was added, and the reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was concentrated to give compound Z27-c (394 mg, 1 mmol). Yield: 100%. MS m / z (ESI): 396 [M+H]+. Step 4: Compound Z27-c (394 mg, 1 mmol) and tert-butyl 4-formylpiperidine-1-carboxylate (213 mg, 1 mmol) were added to 5 ml of DMSO. Then, 3 drops of acetic acid were added, and the mixture was heated under microwave at 50°C and reacted for 30 min. Then, 80 mg of sodium triacetoxyborohydride was added, and the reaction was continued under microwave heating at 50°C with stirring for 1 hour. After the reaction was complete, silica gel was added, and the mixture was stirred for sample loading. Column chromatography was performed using PE / EA (10% to 100%) to give compound Z27-d (355 mg, 0.6 mmol). Yield: 60%. MS m / z (ESI): 593 [M+H]+. Step 5: Compound Z27-d (355 mg, 0.6 mmol) was added to 5 ml of dichloromethane. Then, 2 ml of trifluoroacetic acid was added, and the reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was concentrated to give compound Z27 (295 mg, 0.6 mmol). Yield: 60%. MS m / z (ESI): 493 [M+H]+. Preparation of Intermediate Z28 Z28-d                                             Z28 Step 1: Compound Z28-a (3 g, 14.32 mmol) and KOH (1.61 g, 28.65 mmol) were dissolved in THF (30 mL). Dimethyl sulfate (3.61 g, 28.65 mmol, 2.71 mL) was added dropwise, and the mixture was stirred at room temperature for 1 hour. The solid was filtered off, and the filtrate was concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (40 g, 0% to 20% EA / PE) to give Z28-b (0.7 g, 3.13 mmol, 21.87% yield) as a white solid. MS m / z (ESI): 223.0 [M+H]+. Step 2: Z28-b (0.5 g, 2.24 mmol) and NaHCO3 (375.94 mg, 4.48 mmol) were dissolved in ethanol (15 mL). (5-Fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (486.30 mg, 2.91 mmol) was added. The temperature was raised to 60°C and the mixture was stirred for 1 hour. Water and dichloromethane were added, and extraction was performed three times with DCM:MeOH ~ 10:1. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The crude product was then slurried with ethyl acetate, and filtered to obtain a filter cake. The filter cake was oven-dried to give product Z28-c (0.6 g, 1.69 mmol, 75.71% yield) as a white solid. It was used directly in the next step without purification. MS m / z (ESI): 354.0 [M+H]+. Step 3: Z28-c (80 mg, 225.88 ^mol) and tert-butyl 4-(6-methyl-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridin-2-yl)piperidine-1-carboxylate (99.97 mg, 248.47 pmol) were dissolved in dioxane (5 mL), DMSO (0.5 mL), and water (1 mL). Under argon protection, Pd(dppf)Cl2 (16.53 mg, 22.59 pmol) and K2CO3 (62.44 mg, 451.76 pmol) were added. The temperature was raised to 100°C and the mixture was stirred for 2 hours. The resultant was concentrated under reduced pressure to remove the solvent. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (4 g, 0% to 80% EA / PE) to give Z28-d (30 mg, 54.58 pmol, 24.16% yield) as a brown oil. MS m / z (ESI): 550.3 [M+H]+. Step 4: Z28-d (30 mg, 54.58 pmol) was dissolved in DCM (2 mL). TFA (0.8 mL) was added, and the mixture was stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent. Aqueous sodium bicarbonate solution and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product Z28 (24 mg, 53.39 pmol, 97.82% yield) as a light yellow solid. It was used directly in the next step without purification. MS m / z (ESI): 450.2 [M+H]+. Preparation of Intermediate Z29 Step 1: Z29-a (12 g, 51.01 mmol) and benzylamine (5.47 g, 51.01 mmol) were dissolved in DCM (100 mL). Sodium triacetoxyborohydride (21.62 g, 102.03 mmol) was then added, and the reaction mixture was stirred at room temperature for 18 hours. After the reaction was complete, the mixture was quenched with saturated aqueous sodium bicarbonate solution, and extracted with dichloromethane (200 mL*3). The combined organic phases were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to dryness under reduced pressure to successfully give product Z29-b (16.65 g, 51.01 mmol, 100.00% yield) as an oil. MS m / z (ESI): 327.2 [M+H]+. Step 2: Z29-b (16.65 g, 51.01 mmol) and benzaldehyde (8.12 g, 76.52 mmol) were dissolved in DCM (100 mL). Sodium triacetoxyborohydride (21.62 g, 102.03 mmol) was then added, and the reaction mixture was stirred at room temperature for 18 hours. After the reaction was complete, the mixture was quenched with saturated aqueous sodium bicarbonate solution, and extracted with dichloromethane (200 mL*3). The combined organic phases were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. Purification by CombiFlash column chromatography (120 g, 0% to 45% PE / DCM) successfully gave product Z29-c (6.4 g, 15.37 mmol, 30.12% yield) as a white solid. MS m / z (ESI): 417.3 [M+H]+. Step 3: Z29-c (6.4 g, 15.37 mmol) was dissolved in DCM (35 mL). HCl (4 M in dioxane, 25 mL) was then added thereto. The reaction mixture was stirred at room temperature for 18 hours. After the reaction was complete, the reaction mixture was concentrated, then neutralized with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate (150 mL*3). The combined organic phases were dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to successfully give product Z29-d (4.6 g, 14.54 mmol, 94.62% yield) as a white solid. MS m / z (ESI): 317.2 [M+H]+. Step 4: 3-(5-Bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6- dione (1 g, 2.96 mmol) and Z29-d (1.50 g, 4.73 mmol) were dissolved in toluene (60 mL). Ruphos (275.99 mg, 591.44 pmol) and Ruphos-Pd-G3 (495.26 mg, 591.44 umol) were then added thereto. LiHMDS (1 M in THF, 14.79 mL) was added under a nitrogen atmosphere, and the reaction mixture was stirred at 90°C for 2 hours. After the reaction was complete, the mixture was cooled to room temperature, poured into water (60 mL), and extracted with ethyl acetate (100 mL*3). The combined organic phases were dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. Purification by CombiFlash column chromatography (24 g, 0% to 100% EA / PE) successfully gave product Z29-e (1.1 g, 1.92 mmol, 64.85% yield) as a yellow solid. MS m / z (ESI): 574.2 [M+H]+. Step 5: Z29-e (1.1 g, 1.92 mmol) and Pd / C (300 mg, 10% purity and 50% water) were dissolved in THF (30 mL). The reaction was then stirred at 50°C under a hydrogen balloon condition for 6 hours. The mixture was filtered through Celite. The filter cake was washed with a small amount of methanol, and the filtrate was concentrated to successfully give product Z29 (690 mg, 1.75 mmol, 91.47% yield) as a light yellow solid. MS m / z (ESI): 394.1 [M+H]+. Preparation of Intermediate Z30 Step 1: Z30-a (0.5 g, 1.48 mmol) and 4-N-Boc-4-N-benzylpiperidine (515.26 mg, 1.77 mmol) were dissolved in toluene (10 mL). Ruphos-Pd-G3 (123.81 mg, 147.86 umol) and Ruphos (137.99 mg, 295.72 umol) were added. The mixture was purged with argon three times, then LiHMDS (1 M, 7.39 mL) was added, and the mixture was purged with argon three more times. The temperature was raised to 80°C and stirred for 2 hours. After cooling to room temperature, water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (12 g, 0% to 60% EA / PE) to give Z30-b (0.5 g, 913.00 umol, 61.75% yield) as a light yellow solid. MS m / z (ESI): 548.3 [M+H]+. Step 2: Z30-b (0.4 g, 730.40 pmol) was dissolved in HCl / dioxane (4 M) (10 mL) and stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent and to give a crude product. The crude product was then dissolved in dichloromethane:methanol (10:1), and washed with aqueous sodium bicarbonate solution. The organic phase was dried and concentrated under reduced pressure to remove the solvent to give crude product Z30-c (0.3 g, 670.35 pmol, 91.78% yield) as a white solid. It was used directly in the next step without purification. MS m / z (ESI): 448.2 [M+H]+. Step 3: Z30-c (0.3 g, 670.35 pmol) was dissolved in THF (5 mL). Pd / C (713.39 mg, 670.35 pmol, 10% purity) was added, and the mixture was purged with a hydrogen balloon three times and stirred at room temperature overnight. The catalyst was filtered off, and the mother liquor was concentrated under reduced pressure to give crude product Z30 (0.1 g, 279.79 pmol, 41.74% yield) as an off-white solid, which was used directly in the next step without purification. MS m / z (ESI): 358.2 [M+H]+. Preparation of Intermediate Z31 Z31 Step 1: Z31-a (7 g, 29.90 mmol) and TEA (9.08 g, 89.70 mmol, 12.51 mL) were dissolved in DCM (946.01 pL). Ethyl oxalyl chloride (4.08 g, 29.90 mmol, 3.34 mL) was added at 0°C. The mixture was stirred at room temperature for 1 hour. Water was added, and extraction was performed three times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The crude product was slurried with PE:EA ~ 1:1, and filtered to obtain a filter cake. The filter cake was oven-dried to give product Z31-b (3.5 g, 10.47 mmol, 35.03% yield) as a white solid. MS m / z (ESI): 334.0 [M+H]+. Step 2: Phosphorus oxychloride (4.11 g, 26.82 mmol, 2.50 mL) was added dropwise to a solution of Z31-b (3.5 g, 10.47 mmol) in dioxane (40 mL). The temperature was raised to 110°C and stirred for 8 hours. The mixture was cooled to room temperature and concentrated. The residue was slowly added to saturated aqueous NaHCO3 solution. The precipitated solid was filtered, and the filter cake was washed twice with water. The solid was dried under vacuum to give a crude product. The crude product was then slurried with petroleum ether to give crude product Z31-c (3.3 g, 10.44 mmol, 99.66% yield) as a light brown solid. It was used directly in the next step without purification. MS m / z (ESI): 315.9 [M+H]+. Step 3: Z31-c (3.3 g, 10.44 mmol) was dissolved in DCM (50 mL). m-Chloroperoxybenzoic acid (4.24 g, 20.87 mmol, 85% purity) was added at 0°C, and the mixture was stirred at low temperature for 1 hour. The solid was filtered off, and the mother liquor containing Z31-d (3.4 g, 10.24 mmol, 98.07% yield) was obtained as a light yellow solution, which was used directly in the next step without purification. MS m / z (ESI): 332.0 [M+H]+. Step 4: (5-Fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (3.42 g, 20.47 mmol) and DIEA (3.97 g, 30.71 mmol, 5.35 mL) were dissolved in DCM (1.03 mL). Z31-d (3.4 g, 10.24 mmol) was added at 0°C, and the mixture was stirred at room temperature for 1 hour. Water was added, and extraction was performed three times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (40 g, 0% to 40% EA / PE) to give Z31-e (1.8 g, 4.14 mmol, 40.40% yield) as a light yellow solid. MS m / z (ESI): 435.0 [M+H]+. Step 5: Z31-e (1.8 g, 4.14 mmol) was dissolved in NH3 / MeOH (7 M) (30 mL) and stirred at room temperature overnight. The reaction mixture was filtered directly, and the filter cake was dried to give product Z31-f (1.2 g, 2.95 mmol, 71.43% yield) as a white solid, which was used directly in the next step without purification. MS m / z (ESI): 406.0 [M+H]+. Step 6: Z31-f (0.5 g, 1.23 mmol) was dissolved in phosphorus oxychloride (10 mL). The temperature was raised to 120°C under argon protection and stirred for 4 hours. The resultant was concentrated under reduced pressure to remove the solvent. The pH was then adjusted to greater than 8 with saturated aqueous sodium bicarbonate solution, and extraction was performed three times with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (12 g, 0% to 10% MeOH / DCM) to give Z31-g (0.3 g, 772.81 pmol, 62.78% yield) as a dark green solid. MS m / z (ESI): 388.0 [M+H]+. Step 7: Z31-g (0.15 g, 386.41 pmol) and pinacol 4-(1-Boc-4-piperidinyl)phenylboronate (179.59 mg, 463.69 pmol) were dissolved in dioxane (5 mL) and water (0.5 mL). Under argon protection, Pd(dppf)Cl2 (56.55 mg, 77.28 pmol) and K2CO3 (160.21 mg, 1.16 mmol) were added. The temperature was raised to 100°C and stirred for 2 hours. After cooling to room temperature, water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (4 g, 0% to 10% MeOH / DCM) to give Z31-h (0.1 g, 175.86 pmol, 45.51% yield) as a light yellow solid. MS m / z (ESI): 569.1 [M+H]+. Step 8: Z31-h (0.15 g, 263.79 pmol) was dissolved in DCM (3 mL). TFA (1 mL) was added, and the mixture was stirred at room temperature for 0.5 hours. The resultant was concentrated under reduced pressure. The pH was adjusted to greater than 7 with saturated sodium bicarbonate, and extraction was performed three times with dichloromethane:methanol ~ 10:1. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (4 g, 0% to 10% MeOH / DCM) to give a crude product. The crude product was purified by preparative liquid chromatography (preparative column: 21.2X250 mm C18 column; system: 10 mM NH4HCO3 H2O / acetonitrile; wavelength: 254 / 214 nm; gradient: 5% to 95% acetonitrile change) to give Z31 (15 mg, 32.02 pmol, 12.14% yield) as a light yellow solid. MS m / z (ESI): 469.2 [M+H]+. Preparation of Intermediate Z32 Step 1: Z32-a (3.5 g, 27.02 mmol) and NaHCO3 (6.81 g, 81.05 mmol) were dissolved in MeCN (80 mL). Under argon protection, ethyl 3-bromopyruvate (9.88 g, 40.53 mmol, 6.37 mL) was added. The temperature was raised to 80°C, and the mixture was stirred for 16 hours. The resultant was concentrated under reduced pressure to remove the solvent. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (20 g, 0% to 10% MeOH / DCM) to give a crude product, which was then slurried with petroleum ether and ethyl acetate, and filtered to give product Z32-b (4.5 g, 19.94 mmol, 73.82% yield) as a light yellow solid. MS m / z (ESI): 226.0 [M+H]+. Step 2: Z32-b (4.5 g, 19.94 mmol) and TEA (6.05 g, 59.83 mmol, 8.35 mL) were dissolved in ethanol (100 mL), and (5-fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (6.67 g, 39.89 mmol, 5.33 mL) was added. The temperature was raised to 90°C, and the mixture was stirred for 16 hours. The resultant was concentrated under reduced pressure to remove the solvent and to give a crude product. The residue was separated by CombiFlash column chromatography (80 g, 0% to 40% EA / PE) to give a product, which was then slurried with petroleum ether, and filtered. The filter cake was oven-dried to give product Z32-c (4.5 g, 12.63 mmol, 63.32% yield) as an off-white solid. MS m / z (ESI): 357.1 [M+H]+. Step 3: Z32-c (4 g, 11.22 mmol) was dissolved in DCM (80 mL). Pyridinium tribromide (3.59 g, 11.22 mmol) was added at 0°C, and the mixture was stirred at 0°C for 1 hour. Water was added, and extraction was performed three times with dichloromethane. The combined organic phases were washed with saturated aqueous sodium sulfite solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (40 g, 0% to 10% EA / DCM) to give Z32-d (4 g, 9.19 mmol, 81.87% yield) as a white solid. MS m / z (ESI): 435.0 [M+H]+. Step 4: Z32-d (2 g, 4.60 mmol) was dissolved in NH3 / MeOH (50 mL). The temperature was raised to 50°C in a sealed vessel, and the mixture was stirred for 20 hours. The resultant was concentrated under reduced pressure to remove the solvent and to give crude product Z32-e (1.5 g, 3.69 mmol, 80.36% yield) as a white solid, which was used directly in the next step without purification. MS m / z (ESI): 406.0 [M+H]+. Step 5: Z32-e (1.3 g, 3.20 mmol) was dissolved in phosphorus oxychloride (15 mL). The temperature was raised to 120°C under argon protection, and the mixture was stirred for 4 hours. The resultant was concentrated under reduced pressure to remove the solvent. The pH was then adjusted to greater than 8 with saturated aqueous sodium bicarbonate solution, and extraction was performed three times with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product. The crude product was slurried with petroleum ether and ethyl acetate, and filtered. The filter cake was concentrated to dryness to give product Z32-f (1 g, 2.58 mmol, 80.49% yield) as a white solid. MS m / z (ESI): 388.0 [M+H]+. Step 6: Z32-f (0.5 g, 1.29 mmol) and pinacol 4-(1-Boc-4-piperidinyl)phenylboronate (748.31 mg, 1.93 mmol) were dissolved in dioxane (5 mL) and water (1 mL). Under argon protection, Pd(dppf)Cl2 (94.24 mg, 128.80 pmol) and K2CO3 (534.03 mg, 3.86 mmol) were added. The temperature was raised to 100°C and stirred for 2 hours. The mixture was concentrated under reduced pressure to give a crude product. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (12 g, 0% to 50% EA / PE) to give Z32-g (0.6 g, 1.06 mmol, 81.92% yield) as a light yellow solid. MS m / z (ESI): 569.3 [M+H]+. Step 7: Z32-g (0.1 g, 175.86 pmol) was dissolved in DCM (3 mL). TFA (1 mL) was added, and the mixture was stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent. Dichloromethane and saturated aqueous sodium bicarbonate solution were added, and extraction was performed three times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product Z32 (80 mg, 170.75 pmol, 97.09% yield) as a light yellow solid, which was used directly in the next step without purification. MS m / z (ESI): 469.3 [M+H]+. Preparation of Intermediate Z33 Z32-e                                                Z33-a                                           Z33 Intermediate Z33 was prepared referring to steps 6-7 of Intermediate Z32. MS m / z (ESI): 487.2 [M+H]+. Preparation of Intermediate Z34 Z32-d                                               Z34-a                                           Z34 Intermediate Z34 was prepared referring to steps 6-7 of Intermediate Z32. MS m / z (ESI): 516.2 [M+H]+. Preparation of Intermediate Z35 Z35 Step 1: Tert-butyl 4-(4-bromo-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (762 mg, 3 mmol), bis(pinacolato)diboron (774 mg, 3 mmol), potassium acetate (2.7 g, 9 mmol), and catalyst [1,1'-bis(diphenylphosphinoferrocene]dichloropalladium(II) (146 mg, 0.2 mmol) were added to 5 ml of dioxane. After purging with nitrogen three times, the mixture was heated to 110°C and stirred for 15 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target product was concentrated to give compound tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (890 mg, 2 mmol). Yield: 66%. MS m / z (ESI): 446 [M+H]+. Step 2:   Tert-butyl   4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)- 1H-pyrazol-1-yl)piperidine-1-carboxylate (890 mg, 2 mmol), 8-bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (792 mg, 3 mmol), potassium carbonate (828 mg, 6 mmol), catalyst [1,1'-bis(diphenylphosphinoferrocene]dichloropalladium(II) (146 mg, 0.2 mmol), and 1 ml of water were sequentially added to 5 ml of dioxane. After purging with nitrogen three times, the mixture was heated to 100°C and stirred for 15 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target product was concentrated to give compound tert-butyl 4-(4-(1-chloro-5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino) imidazo[1,5-c]pyrimidin-8-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (952 mg, 1.5 mmol). Yield: 75%. MS m / z (ESI): 636 [M+H]+. Step 3: Tert-butyl 4-(4-(1-chloro-5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino) imidazo[1,5-c]pyrimidin-8-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (952 mg, 1.5 mmol) was added to a mixed solution of 5 ml of dichloromethane and 1 ml of trifluoroacetic acid. The mixture was stirred at room temperature for 1 hour, and then concentrated and dried under oil pump vacuum to give compound Z35 (802 mg, 0.5 mmol). Yield: 100%. MS m / z (ESI): 536 [M+H]+. Preparation of Intermediate Z36 Z36-b Step     1:     8-Bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5- c]pyrimidin-5-amine (0.6 g, 1.51 mmol) and 2-fluoro-6-methylpyridine-5-boronic acid (350.68 mg, 2.26 mmol) were dissolved in dioxane (15 mL), water (2 mL), and DMSO (1 mL). Under argon protection, Pd(dppf)Cl2 (110.41 mg, 150.89 gmol) and K2CO3 (625.63 mg, 4.53 mmol) were added. The temperature was raised to 100°C, and the mixture was stirred for 2 hours. After cooling to room temperature, water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (12 g, 0% to 30% EA / PE) to give Z36-a (0.55 g, 1.29 mmol, 85.20% yield) as a light brown solid. MS m / z (ESI): 428.1 [M+H]+. Step 2: Z36-a (100 mg, 233.74 gmol) and tert-butyl piperazine-1-carboxylate (217.67 mg, 1.17 mmol) were dissolved in NMP (3 mL). DIEA (90.63 mg, 701.21 pmol, 122.14 gL) was added, and the mixture was heated under microwave to 200°C and stirred for 2 hours. After cooling to room temperature, Boc2O (153.04 mg, 701.21 gmol) was added dropwise, and the mixture was stirred at room temperature for 0.5 hours. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (4 g, 0% to 30% EA / DCM) to give Z36-b (80 mg, 134.66 gmol, 57.61% yield) as a light yellow solid. MS m / z (ESI): 594.3 [M+H]+. Step 3: Z36-b (80 mg, 134.66 gmol) was dissolved in DCM (2 mL). TFA (1 mL) was added, and the mixture was stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent. Dichloromethane and saturated aqueous sodium bicarbonate solution were added, and extraction was performed three times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product Z36 (60 mg, 121.47 gmol, 90.20% yield) as a light yellow solid, which was used directly in the next step without purification. MS m / z (ESI): 494.2 [M+H]+. Preparation of Intermediate Z37 Step 1:    6-Bromo-3-iodo-1-methyl-1H-indazole (5.2 g, 15.43 mmol) and 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (7.41 g, 17.75 mmol) were dissolved in 1,4-dioxane (80 mL) and water (20 mL). Pd(dppf)Cl2 (1.13 g, 1.54 mmol) and Cs2CO3 (10.06 g, 30.86 mmol) were then added thereto, and the mixture was purged with nitrogen. The reaction mixture was stirred at 100°C for 3 hours. After the reaction was complete, the mixture was cooled to room temperature, quenched with water, and extracted with ethyl acetate (120 mL*3). The combined organic phases were dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. Purification by CombiFlash column chromatography (24 g, 0% to 100% EA / PE) successfully gave product Z37-a (4.9 g, 63.45% yield) as a white solid. MS m / z (ESI): 500.1 [M+H]+. Step 2: Z37-a (1.5 g, 3.00 mmol) and tert-butyl piperazine-1-carboxylate (837.48 mg, 4.50 mmol) were dissolved in dioxane (15 mL). Under argon protection, Pd2(dba)3 (274.50 mg, 299.77 pmol), X-Phos (285.81 mg, 599.54 pmol), and Cs2CO3 (1.95 g, 6.00 mmol) were added. The temperature was raised to 100°C and stirred overnight. The resultant was concentrated under reduced pressure to remove the solvent. Water and ethyl acetate were then added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (20 g, 0% to 30% EA / PE) to give Z37-b (1.7 g, 2.81 mmol, 93.62% yield) as a light brown solid. MS m / z (ESI): 606.3 [M+H]+. Step 3: Z37-b (1.7 g, 2.81 mmol) was dissolved in ethanol (30 mL) and THF (30 mL). Pd / C (297.50 mg, 280.66 pmol, 10% purity) was added, and the mixture was purged with a hydrogen balloon three times. The mixture was stirred at room temperature overnight. The catalyst was filtered off, and the mother liquor was concentrated under reduced pressure to give crude product Z37-c (1.1 g, 2.57 mmol, 91.68% yield) as a light yellow solid. It was used directly in the next step without purification. MS m / z (ESI): 428.2 [M+H]+. Step 4: Z37-c (0.5 g, 1.17 mmol) was dissolved in DCM (6 mL). TFA (2 mL) was added, and the mixture was stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent. Dichloromethane and saturated aqueous sodium bicarbonate solution were added, and extraction was performed three times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product Z37 (0.25 g, 763.64 pmol, 65.29% yield) as a light yellow solid. It was used directly in the next step without purification. MS m / z (ESI): 328.2 [M+H]+. Preparation of Intermediate Z38 Z36-a                                                             Z38-a Z38 Step 1: Z36-a (150 mg, 350.60 gmol) and 4-(dimethoxymethyl)piperidine (279.12 mg, 1.75 mmol) were dissolved in NMP (3 mL). DIEA (135.94 mg, 1.05 mmol, 183.20 uL) was added, and the mixture was heated under microwave to 200°C and stirred for 1 hour. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (4 g, 0% to 40% EA / PE) to give Z38-a (150 mg, 264.53 pmol, 75.45% yield) as a light yellow solid. MS m / z (ESI): 567.3 [M+H]+. Step 2: Z38-a (150 mg, 264.53 pmol) was dissolved in DCM (3 mL). TFA (1 mL) was added, and the mixture was stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent. Dichloromethane and saturated aqueous sodium bicarbonate solution were added, and extraction was performed three times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product Z38 (0.1 g, 191.94 umol, 72.56% yield) as a light yellow solid, which was used directly in the next step without purification. MS m / z (ESI): 521.2 [M+H]+. Preparation of Intermediate Z39 Using Z37-a as starting material and referring to the method of Z37, Z39 was prepared. MS m / z (ESI): 424.3 [M+H]+. Preparation of Intermediate Z40 Using Z37-a as starting material and referring to the method of Z37, Z40 was prepared. MS m / z (ESI): 426.3 [M+H]+. Preparation of Intermediate Z41 Step 1:   Compound 8-bromo-1-chloro-N-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl] imidazo[1,5-c]pyrimidin-5-amine (150 mg, 377.24 umol) and tert-butyl 3-hydroxy-3-[6-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]azetidine-1-carboxylate (147.23 mg, 377.24 umol) were dissolved in dioxane (5 mL) and water (0.5 mL). Under argon protection, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (276.03 mg, 377.24 umol) and potassium carbonate (52.14 mg, 377.24 umol) were added sequentially. The temperature was raised to 95°C, and the mixture was stirred overnight. Reaction progress was monitored by LC-MS. The reaction mixture was concentrated to dryness under reduced pressure, and purified by silica gel column chromatography (MeOH:DCM = 0% to 10%) to give Z41-a (110 mg, 189.32 umol, 50.19% yield) as a yellow solid. MS m / z (ESI): 581 [M+H]+. Step 2: Z41-a (113.11 mg, 194.68 umol) was dissolved in dichloromethane (5 mL). Trifluoroacetic acid (1.83 g, 16.08 mmol, 1 mL) was added with stirring at room temperature, and the mixture was stirred at room temperature for 2 hours with the reaction progress monitored by LC-MS. The reaction mixture was concentrated to dryness under reduced pressure, added with saturated sodium carbonate solution, extracted with EA (30 mL*2), dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure to give Z41 (60 mg, 124.76 umol, 64.09% yield) as a yellow solid. MS m / z (ESI): 481 [M+H]+. Preparation of Intermediate Z42 Step 1: 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (500 mg, 2.58 mmol), tert-butyl      4-hydroxypiperidine-1-carboxylate      (1.04      g,      5.15 mmol),     and cyanomethylenetributylphosphorane (1.24 g, 5.15 mmol) were dissolved in toluene (10 mL). After purging with argon, the mixture was stirred at 90°C for 16 hours with product generated. The reaction mixture was concentrated to dryness under reduced pressure, and the concentrate was purified by combiflash (EA:PE = 0% to 40%) to give product Z42-a (550 mg, crude) as a yellow oil. MS m / z (ESI): 378.3 [M+H]+. Step 2:     8-Bromo-1-chloro-N-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl]imidazo[1,5- c]pyrimidin-5-amine (150 mg, 377.24 umol) and Z42-a (426.98 mg, 1.13 mmol) were dissolved in a mixed solution of 1,4-dioxane (10 mL), H2O (2 mL), and DMSO (0.5 mL). PdCl2(dppf) (82.81 mg, 113.17 pmol) and potassium carbonate (260.69 mg, 1.89 mmol) were added. After purging with argon, the mixture was stirred at 95°C for 3 hours, and the starting material was completely reacted. The reaction mixture was concentrated to dryness under reduced pressure to give a crude product, which was purified by combiflash (EA:PE = 0% to 40%) to give product Z42-b (105 mg, yield: 49.00%) as a yellow oil. MS m / z (ESI): 512.2 [M-56+H]+. Step 3: Z42-b (105 mg, 184.85 pmol) was dissolved in DCM (5 mL). Trifluoroacetic acid (21.08 mg, 184.85 pmol, 1 mL) was added, and the mixture was stirred at room temperature (25°C) for 2 hours, and the starting material was completely reacted. The reaction mixture was concentrated to dryness under reduced pressure. Triethylamine (1 ml) was added to basify the product, and the resultant was further concentrated to dryness under reduced pressure to give crude product Z42 (86 mg, crude) as a yellow oil, which was used directly in the next step without further purification. MS m / z (ESI): 468.1 [M+H]+. Preparation of Intermediate Z43 Z43 Following the above route and referring to the preparation method of Z42, Z43 was obtained. MS m / z (ESI): 468.1 [M+H]+. Preparation of Intermediate Z44 Z44 Following the above route and referring to the preparation method of Z42, Z44 was obtained. MS m / z (ESI): 468.1 [M+H]+. Preparation of Intermediate Z45 Z45-d Z45-e Z45 Step 1:  8-Bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5- amine (2 g, 5.51 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (2.04 g, 6.61 mmol) were dissolved in 1,4-dioxane (30 mL) and water (6 mL). Pd(dppf)Cl2 (805.88 mg, 1.10 mmol) and K2CO3 (2.28 g, 16.52 mmol) were then added. The reaction mixture was stirred at 100°C for 3 hours. After the reaction was complete, the resultant was concentrated under reduced pressure to remove the solvent. The residue was separated by CombiFlash column chromatography (12 g, 0% to 100% EA / PE) to successfully give product Z45-a (2.2 g, 85.82% yield) as a light yellow solid. MS m / z (ESI): 466.2 [M+H]+. Step 2: Z45-a (2.2 g, 4.73 mmol) was dissolved in MeOH (40 mL). Pd(OH)2 / C (774.70 mg, 1.26 mmol, 20% purity) was then added, and the reaction mixture was stirred at room temperature under hydrogen atmosphere for 18 hours. After the reaction was complete, the mixture was filtered, and the filtrate was concentrated to give crude product Z45-b (2.1 g, 95.04% yield) as a light yellow solid. MS m / z (ESI): 468.2 [M+H]+. Step 3: Compound Z45-b (2.1 g, 4.49 mmol) was dissolved in DMF (40 mL). NCS (599.78 mg, 4.49 mmol) was added under ice bath, and the reaction was allowed to warm to room temperature under ice bath with stirring. The reaction mixture was stirred overnight. After the starting material was completely reacted, the reaction mixture was directly concentrated to dryness under reduced pressure, and purified by CombiFlash column chromatography (12 g, 0% to 40% EA / DCM) to give product Z45-c (2.1 g, 93.14% yield) as an off-white solid. MS m / z (ESI): 502.2 [M+H]+. Step 4: Z45-c (2.1 g, 4.18 mmol) was dissolved in DCM (30 mL). HCl (4 M in dioxane, 10 mL) was then added thereto, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction mixture was concentrated, and then neutralized with saturated aqueous sodium bicarbonate solution with a solid precipitated. The solid was filtered, washed twice with water, and then washed twice with a small amount of methanol. The filter cake was dried under vacuum to give crude product Z45-d (1.3 g, 77.33% yield) as a light yellow solid. MS m / z (ESI): 402.1 [M+H]+. Step 5: Z45-d (500 mg, 1.24 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (1.49 g, 7.47 mmol) were dissolved in DMSO (9 mL) and EtOH (3 mL). NaBH3CN (781.88 mg, 12.44 mmol) and AcOH (373.58 mg, 6.22 mmol) were then added, and the reaction mixture was stirred under microwave at 85°C for 0.7 hours. After the reaction was complete, the reaction mixture was poured into water, and extracted with dichloromethane (50 mL*3). The combined organic phases were dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to dryness under reduced pressure. Purification by CombiFlash column chromatography (24 g, 0% to 100% THF / PE) successfully gave product Z45-e (620 mg, 85.17% yield) as a light yellow solid. MS m / z (ESI): 585.3 [M+H]+. Step 6: Z45-e (620 mg, 1.06 mmol) was dissolved in DCM (20 mL). CF3COOH (120.82 mg, 1.06 mmol, 6 mL) was then added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was concentrated, and neutralized with aqueous sodium bicarbonate solution with a solid precipitated. The solid was filtered, and the filter cake was washed with water and dichloromethane. The filter cake was dried under vacuum to give product Z45 (420 mg, 81.73% yield) as a light yellow solid. MS m / z (ESI): 485.2 [M+H]+. Preparation of Intermediate Z46 Z46 Step    1:    4-Bromo-1H-pyrazole (7 g, 47.63 mmol) and tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (9.96 g, 50.01 mmol) were dissolved in DMSO (100 mL), and Cs2CO3 (31.04 g, 95.26 mmol) was added. The reaction mixture was stirred at 80°C for 4 hours. The reaction mixture was filtered, and washed. The filtrate was diluted with EA, washed three times with saturated brine, and concentrated under reduced pressure. The crude product was separated by CombiFlash column chromatography (0% to 70% EA / PE) to obtain tert-butyl 4-(4-bromopyrazol-1-yl)-3-hydroxy-piperidine-1-carboxylate (15.46 g, 93.76% yield) as a yellow solid. MS m / z (ESI): 290.0 [M+H-56]+. Step 2: Tert-butyl 4-(4-bromopyrazol-1-yl)-3-hydroxy-piperidine-1-carboxylate (2.9 g, 8.38 mmol) was dissolved in DCM (20 mL), and Dess-Martin oxidant (5.33 g, 12.56 mmol) was added. The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was poured into water, neutralized by adding saturated NaHCO3 solution, filtered, washed, extracted, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was separated by CombiFlash column chromatography (0% to 70% EA / PE) to obtain tert-butyl 4-(4-bromopyrazol-1-yl)-3-oxo-piperidine-1-carboxylate (2.4 g, 83.24% yield) as a yellow solid. MS m / z (ESI): 288.0 [M+H-56]+. Step 3: Tert-butyl 4-(4-bromopyrazol-1-yl)-3-oxo-piperidine-1-carboxylate (3.95 g, 11.48 mmol) was dissolved in DCM (40 mL), cooled to -78°C, and N-ethyl-N-(trifluoro-sulfanyl)ethanamine (5.55 g, 34.43 mmol, 4.55 mL) was added. The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was poured into water, extracted with DCM, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was separated by CombiFlash column    chromatography    (0%    to    70%    EA / PE)    to    obtain    tert-butyl 4-(4-bromopyrazol-1-yl)-3,3-difluoro-piperidine-1-carboxylate (2.5 g, 59.49% yield) as a yellow solid. MS m / z (ESI): 310.0 [M+H-56]+. Step 4:     8-Bromo-1-chloro-N-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl]imidazo[1,5- c]pyrimidin-5-amine (360 mg, 905.37 gmol) and tert-butyl  4-(4-bromopyrazol-1-yl)-3,3- difluoro-piperidine-1-carboxylate (663.09 mg, 1.81 mmol) were dissolved in DME (15 mL) and water (1.5 mL), and palladium acetate (40.65 mg, 181.07 pmol), di(1-adamantyl)butylphosphine (129.84 mg, 362.15 pmol), K2CO3 (501 mg, 3.62 mmol), and (Pin)2B2 (919.63 mg, 3.62 mmol) were added. The reaction mixture was reacted at 70°C under argon atmosphere for 6 hours. The reaction mixture was poured into water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was separated by CombiFlash column chromatography (0% to 100% EA / PE) to obtain tert-butyl 4-[4-[1-chloro-5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]imidazo[1,5-c]pyrimidin-8-yl]pyrazol-1-yl]-3,3-difluoro-piperidine-1-carboxylate (177 mg, 32.37% yield) as a yellow solid. MS m / z (ESI): 548.2 [M+H-56]+. Step 5:    Tert-butyl 4-[4-[1-chloro-5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino] imidazo[1,5-c]pyrimidin-8-yl]pyrazol-1-yl]-3,3-difluoro-piperidine-1-carboxylate (177 mg, 293.04 pmol) was dissolved in DCM (15.00 mL), and trifluoroacetic acid (3 mL) was added. The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, neutralized with NaHCO3 solution, extracted with DCM, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product, 1-chloro-8-[1-(3,3-difluoropiperidin-4-yl)pyrazol-4-yl]-N-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)meth yl]imidazo[1,5-c]pyrimidin-5-amine (130 mg, 88.04% yield), was directly used in the next step. MS m / z (ESI): 504.2 [M+H]+. Preparation of Intermediate Z47 Z47-a                                            Z47-b                                                    247 Step     1:     8-Bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3-c] pyrimidin-5-amine (0.8 g, 2.20 mmol) was dissolved in THF (30 mL), and n-BuLi (2.5 M, 4.39 mL) was added dropwise at -78°C. The reaction mixture was stirred for 1 hour. Triisopropyl borate (4.96 g, 26.36 mmol, 6.08 mL) was slowly added dropwise, and the reaction mixture was stirred for 1 hour. The reaction mixture was quenched with 1N HCl, stirred at room temperature for 0.5 hours, then extracted with ethyl acetate twice, and concentrated under reduced pressure. The residue was purified by combiflash with DCM:MeOH=10:1 to obtain Z47-a (22 mg, 66.85 pmol, 3.04% yield) as a yellow oil. MS m / z (ESI): 412.1 [M+H]+. Step 2: Under argon atmosphere, tert-butyl 4-(6-bromopyridazin-3-yl)piperidine-1- carboxylate (100 mg, 292.20 pmol), Z47-a (400.67 mg, 438.30 pmol), Pd(dppf)Cl2 (21.38 mg, 29.22 pmol), potassium carbonate (121.15 mg, 876.60 pmol), 1,4-dioxane (4 mL), and water (1 mL) were heated to 115°C and reacted for 2 hours. The reaction mixture was filtered, the filtrate was separated to obtain the aqueous layer, which was then concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate=30%:70%) to obtain crude Z47-b (135 mg, 29.64 pmol, 10.14% yield) as a yellow solid. MS m / z (ESI): 547.3 [M+H]+. Step 3: At room temperature, Z47-b (125 mg, 228.69 pmol), TFA (0.5 mL), and DCM (0.5 mL) were mixed and reacted for 1 hour. The reaction mixture was concentrated to give a crude product. The crude product was dissolved in DCM:MeOH=10:1, and adjusted to pH=7 to 8 by adding saturated sodium bicarbonate solution. The organic layer was collected, dried over anhydrous sodium sulfate, and concentrated to give Z47 (100 mg, 223.97 pmol, 97.94% yield) as a yellow oil. The crude product was directly used in the next step. MS m / z (ESI): 447.2 [M+H]+. Preparation of Intermediate Z48 Z48-a                                      Z48 Step 1: Tert-butyl 4-formyl-3,6-dihydropyridine-1(2H)-carboxylate (5 g, 23.44 mmol) was dissolved in ethanol (50 mL). Hydroxylamine hydrochloride (2.45 g, 35.28 mmol) and pyridine (2.45 g, 31.03 mmol, 2.50 mL) were then added thereto, and the reaction mixture was stirred at room temperature for 6 hours. After the reaction was complete, water and ethyl acetate were added, which was extracted with ethyl acetate (150 mL*3), and washed with saturated brine (100 mL). The combined organic phases were dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to give a crude product. Purification by CombiFlash column chromatography (40 g, 0% to 10% DCM / MeOH) successfully gave product tert-butyl (E)-4-((hydroxyimino)methyl)-3,6-dihydropyridine-1(2H)-carboxylate (1.2 g, 22.42% yield) as a white solid. MS m / z (ESI): 129.2 [M-100+H]+. Step 2: Tert-butyl (E)-4-((hydroxyimino)methyl)-3,6-dihydropyridine-1(2H)-carboxylate (559.47 mg, 2.45 mmol) and 1-chloro-8-ethyl-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (280 mg, 816.91 pmol) were dissolved in methanol (60 mL) and THF (15 mL). [Bis(trifluoroacetoxy)iodo]benzene (1.23 g, 2.86 mmol) was then added thereto, and the reaction mixture was stirred at room temperature for 20 hours. After the reaction was complete, the reaction was quenched with water, and the resultant was extracted with ethyl acetate (70 mL*3). The combined organic phases were dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to dryness under reduced pressure. Purification by CombiFlash column chromatography (12 g, 0% to 50% EA / PE) successfully gave product Z48-a (87 mg, 18.72% yield) as a light yellow solid. MS m / z (ESI): 569.2 [M+H]+. Step 3: Z48-a (87 mg, 152.89 pmol) was dissolved in DCM (4 mL). CF3COOH (1.05 g, 9.17 mmol, 1 mL) was then added thereto. The reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was neutralized with saturated sodium bicarbonate, and extracted with dichloromethane (70 mL*3). The combined organic phases were dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to dryness under reduced pressure to successfully give product Z48 (65 mg, 90.66% yield) as a light yellow solid. MS m / z (ESI): 469.2 [M+H]+. Preparation of Intermediate Z49 Z49 Compound       8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3- c]pyrimidin-5-amine (726 mg, 2 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzaldehyde (464 mg, 2 mmol), potassium carbonate (414 mg, 3 mmol), and catalyst [1,1'-bis(diphenylphosphinoferrocene]dichloropalladium(II) (146 mg, 0.2 mmol) were added to a mixed solution of 5 ml of 1,4-dioxane and 1 ml of water. After purging with nitrogen three times, the mixture was heated to 100°C and stirred for 5 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target product was concentrated to give Z49 (391 mg, 1 mmol). Yield: 50%. MS m / z (ESI): 390 [M+H]+. Preparation of Intermediate Z50 Pd (dppf)CI2,NaHCO3 Dioxane / H20,100°C,1.5h CN Z50 Intermediate Z50 was obtained referring to the preparation method of Z49. MS m / z (ESI): 428.1 [M+H]+. Preparation of Intermediate Z51 Pd (dppf)CI2,NaHCO3 Dioxane / H20,100°C,1.5h Intermediate Z51 was obtained referring to the preparation method of Z49. MS m / z (ESI): 437.1 [M+H]+. Preparation of Intermediate Z52 Intermediate Z52 was obtained referring to the preparation method of Z49. MS m / z (ESI): 404.1 [M+H]+. Preparation of Intermediate Z53 Z53 Step     1:     Tert-butyl 4-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-benzimidazol-5-yl] piperazine-1-carboxylate (240 mg, 541.16 pmol) was dissolved in DCM (15 mL), and trifluoroacetic acid (3 mL) was added. The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, neutralized to basicity with NaHCO3 solution, extracted with dichloromethane (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under        reduced        pressure.        The        obtained        crude        product, 3-(3-methyl-2-oxo-5-piperazin-1-yl-benzimidazol-1-yl)piperidine-2,6-dione (180 mg, 96.87% yield), was used directly in the next step. MS m / z (ESI): 344.2 [M+H]+. Step 2: 3-(3-Methyl-2-oxo-5-piperazin-1-yl-benzimidazol-1-yl)piperidine-2,6-dione (180 mg, 524.20 gmol) and tert-butyl 3,3-difluoro-4-oxopiperidine-1-carboxylate (185 mg, 786.30 gmol) were dissolved in toluene (6 mL) and acetonitrile (3 mL). Sodium acetate (175.40 mg, 1.31 mmol) and acetic acid (293.72 mg, 4.89 mmol) were added. The reaction mixture was stirred at 120°C for 20 hours. The reaction mixture was poured into water, neutralized to basicity with saturated NaHCO3 solution, extracted with dichloromethane (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crude product, tert-butyl 4-[4-[1-(2,6-dioxo-3-piperidinyl)-3-methyl-2-oxo-benzimidazol-5-yl]piperazin-1-yl]-3,3-difluoropiperidine-1-carboxylate (280 mg, 94.94% yield), was used directly in the next step. MS m / z (ESI): 561.3 [M+H]+. Step 3:     Tert-butyl    4-[4-[1-(2,6-dioxo-3-piperidinyl)-3-methyl-2-oxo-benzimidazol-5- yl]piperazin-1-yl]-3,3-difluoropiperidine-1-carboxylate (280 mg, 499.47 pmol) was dissolved in dichloroethane (10 mL) and methanol (10 mL). AcOH (73.32 mg, 1.22 mmol) and NaBH3CN (156.94 mg, 2.50 mmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was poured into water, neutralized with saturated NaHCO3, extracted with dichloromethane (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crude product, tert-butyl 4-[4-[1-(2,6-dioxo-3-piperidinyl)-3-methyl-2-oxo-benzimidazol-5-yl]piperazin-1-yl]-3,3-difluoropiperidine-1-carboxylate (100 mg, 35.59% yield), was used directly in the next step. MS m / z (ESI): 563.3 [M+H]+. Step 4: Tert-butyl 4-[4-[1-(2,6-dioxo-3-piperidinyl)-3-methyl-2-oxo-benzimidazol-5-yl]piperazin-1-yl]-3,3-difluoropiperidine-1-carboxylate (100 mg, 177.74 umol) was dissolved in DCM (15 mL), and trifluoroacetic acid (3 mL) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, neutralized to basicity with NaHCO3 solution, extracted with dichloromethane (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crude product Z53 (80 mg, 97.32% yield) was used directly in the next step. MS m / z (ESI): 463.2 [M+H]+. Preparation of Intermediate Z54 Step       1:       Compound       8-bromo-1-fluoro-N-((5-fluoro-2,3-dihydrobenzofuran-4- yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (191 mg, 0.5 mmol) and ethynyl(triisopropyl)silane (0.46 g, 2.52 mmol) were dissolved in THF (5 mL). Copper(I) iodide (29 mg, 0.15 mmol), Pd(PPh3)2Cl2 (71 mg, 0.1 mmol), and diisopropylamine (0.51 g, 5.03 mmol, 0.69 mL) were then added. After purging with nitrogen three times, the reaction mixture was reacted at 75°C under argon protection for 48 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target product was concentrated to give compound 1-fluoro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-((triisopropylsilyl)ethynyl)imidazo[1,5-c]pyrimidin-5-amine (170 mg, 0.35 mmol). Yield: 70%. MS m / z (ESI): 483 [M+H]+. Step      2:      Compound      1-fluoro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8- ((triisopropylsilyl)ethynyl)imidazo[1,5-c]pyrimidin-5-amine (170 mg, 0.35 mmol) was added to 0.5 M TBAF-THF solution (3 mL) and stirred at room temperature for 2 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target product was concentrated to give compound 8-ethynyl-1-fluoro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (65 mg, 0.2 mmol). Yield: 57%. MS m / z (ESI): 327 [M+H]+. Step 3:   Compound   8-ethynyl-1-fluoro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl) imidazo[1,5-c]pyrimidin-5-amine (65 mg, 0.2 mmol) and tert-butyl 4-azidopiperidine-1- carboxylate (130 mg, 0.58 mmol) were dissolved in t-BuOH (5 mL) and water (1 mL). Sodium ascorbate (12 mg, 70 pmol) and CuSO<5H2O (7 mg, 29 gmol) were added. After purging with argon, the mixture was stirred at 70°C for 12 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target product was concentrated to give compound tert-butyl 4-(4-(1-fluoro-5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino)imidazo[1,5-c]pyrimidin-8-yl)-1H-1,2,3-triazol-1-yl)piperidine-1-carboxylate (10 mg, 18 ^mol). Yield: 9%. MS m / z (ESI): 553 [M+H]+. Step 4:   Compound tert-butyl 4-(4-(1-fluoro-5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl) methyl)amino)imidazo[1,5-c]pyrimidin-8-yl)-1H-1,2,3-triazol-1-yl)piperidine-1-carboxylate (10 mg, 18 pmol) was added to a mixed solvent of 2 ml of dichloromethane and 0.5 ml of trifluoroacetic acid. After stirring at room temperature for 1 hour, the solvent was removed by rotary evaporation under oil pump vacuum to give crude compound Z54 (8.1 mg, 18 pmol). Yield: 100%. MS m / z (ESI): 453 [M+H]+. Preparation of Intermediate Z55 Following the above synthetic route and referring to the preparation method of Z54, Z55 was obtained. MS m / z (ESI): 436.2 [M+H]+. Preparation of Intermediate Z56 Step 1:    4,5-Dibromo-2H-triazole (5 g, 22.04 mmol) and tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate (6.46 g, 23.14 mmol) were dissolved in DMF (110 mL). Cs2CO3 (21.54 g, 66.12 mmol) was added. The reaction mixture was stirred at 100°C overnight. The reaction mixture was poured into water, extracted with ethyl acetate (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crude product was separated by CombiFlash (0% to 50% EA / PE) to give product tert-butyl 4-(4,5-dibromotriazol-2-yl)piperidine-1-carboxylate (6.27 g, 69.37% yield) as a colorless oil. MS m / z (ESI): 352.9 [M+H-56]+. Step 2: Tert-butyl 4-(4,5-dibromotriazol-2-yl)piperidine-1-carboxylate (6.27 g, 15.29 mmol) was dissolved in tetrahydrofuran (45 mL), cooled to -78°C, and n-BuLi (2.5 M, 6.07 mL) was slowly added dropwise. The reaction mixture was stirred at -78°C for 1 hour. NH4Cl solution was added to quench the reaction. Extraction was performed with ethyl acetate (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was separated by CombiFlash (0% to 60% EA / PE) to give tert-butyl 4-(4-bromotriazol-2-yl)piperidine-1-carboxylate (980 mg, 19.35% yield) as an anhydrous oil. MS m / z (ESI): 275.0 [M+H-56]+. Step 3: Tert-butyl 4-(4-bromotriazol-2-yl)piperidine-1-carboxylate (490 mg, 1.48 mmol) was dissolved in THF (20 mL), cooled to -78°C, and n-BuLi (2.5 M, 769.30 pL) was slowly added dropwise. The reaction mixture was stirred at -78°C for 0.5 h, then 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (551 mg, 2.96 mmol) was added. The reaction mixture was slowly warmed to room temperature and stirred for another 2 hours. The reaction mixture was cooled to 0°C, and saturated NH4Cl solution was added dropwise to quench the reaction. The resultant was extracted with ethyl acetate (30 mLx3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)triazol-2-yl]piperidine-1-carboxylate (550 mg, 98.28% yield), which was used directly in the next step. MS m / z (ESI): 197.1 [M+H-182]+. Step 4:     8-Bromo-1-chloro-N-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl]imidazo[1,5- c]pyrimidin-5-amine (100 mg, 251.49 pmol) and tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)triazol-2-yl]piperidine-1-carboxylate (114.16 mg, 301.79 pmol) were dissolved in dioxane (12 mL) and water (2 mL). PdCl2(dppf) (18.40 mg, 25.15 pmol) and potassium carbonate (69.51 mg, 502.98 pmol) were added. The reaction mixture was stirred at 100°C overnight. The reaction mixture was poured into water, extracted with ethyl acetate (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was separated by CombiFlash column chromatography (0% to 80% EA / PE) to give product tert-butyl 4-[4-[1-chloro-5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino] imidazo[1,5-c]pyrimidin-8-yl]triazol-2-yl]piperidine-1-carboxylate (22 mg, 15.37% yield) as a yellow solid. MS m / z (ESI): 513.2 [M+H-56]+. Step 5:   Tert-butyl   4-[4-[1-chloro-5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino] imidazo[1,5-c]pyrimidin-8-yl]triazol-2-yl]piperidine-1-carboxylate (22 mg, 38.66 pmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (3 mL) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, neutralized to basicity with NaHCO3 solution, extracted with dichloromethane (30 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crude product Z56 (18 mg, 99.29% yield) was used directly in the next step. MS m / z (ESI): 469.2 [M+H]+. Preparation of Intermediate Z57 Z57 Step 1:    Compound   8-bromo-1-fluoro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl) imidazo[1,5-c]pyrimidin-5-amine (570 mg, 1.5 mmol), n-butyldi(1-adamantyl)phosphine (214 mg, 598 pmol), diacetoxypalladium (67 mg, 300 pmol), K2CO3 (620 mg, 4.48 mmol), and (Pin)2B2 (1140 mg, 4.48 mmol) were sequentially added to a mixed solution of DME (100 mL) and water (10 mL). After purging with nitrogen three times, the reaction mixture was reacted at 70°C under argon protection for 20 hours. After the reaction was complete, silica gel was directly added to the mixture, which was stirred for sample loading. Column chromatography was performed using 30% to 100% PE / EA. The target      product      was      concentrated      to      give      compound      tert-butyl 4-(3-(1-fluoro-5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino)imidazo[1,5-c]pyrimidin-8-yl)-1H-1,2,4-triazol-1-yl)piperidine-1-carboxylate (83 mg, 0.15 mmol). Yield: 10%. MS m / z (ESI): 553 [M+H]+. Step 2:    Compound tert-butyl    4-(3-(1-fluoro-5-(((5-fluoro-2,3-dihydrobenzofuran-4- yl)methyl)amino)imidazo[1,5-c]pyrimidin-8-yl)-1H-1,2,4-triazol-1-yl)piperidine-1-carboxylate (83 mg, 0.15 mmol) was added to a mixed solution of 5 ml of dichloromethane and 1 ml of trifluoroacetic acid. The mixture was stirred at room temperature for 1 hour, and then concentrated and dried under oil pump vacuum to give compound Z57 (68 mg, 0.15 mmol). Yield: 100%. MS m / z (ESI): 453 [M+H]+. Preparation of Intermediate Z58 Step     1:     8-Bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3-c] pyrimidin-5-amine (1 g, 2.75 mmol) was dissolved in THF (30 mL). At -78°C, n-BuLi (2.5 M, 5.49 mL) was added dropwise, and the reaction was carried out for 1 hour. Isopropoxy pinacol borate (6.13 g, 32.95 mmol, 6.72 mL) was slowly added dropwise, and the mixture was stirred at low temperature for 1 hour. The reaction mixture was quenched with saturated ammonium chloride solution, stirred at room temperature for 0.5 hours, and then extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The crude product was purified by preparative liquid chromatography (preparative column: 21.2x250 mm C18 column; system: 10 mM FA H2O / acetonitrile; wavelength: 254 / 214 nm; gradient: 5%-95% acetonitrile change) to give Z58-a (0.2 g, 607.73 pmol, 22.13% yield) as a light yellow solid. MS m / z (ESI): 330.1 [M+H]+. Step 2: Z58-a (198.72 mg, 603.85 pmol) and tert-butyl 4-(3-bromo-1H-1,2,4-triazol-1-yl) piperidine-1-carboxylate (200 mg, 603.85 pmol) were dissolved in dioxane (8 mL) and water (1 mL). Under argon protection, Pd(dppf)Cl2 (44.18 mg, 60.38 pmol) and K2CO3 (166.92 mg, 1.21 mmol) were added. The temperature was raised to 120°C, and the mixture was stirred for 2 hours. The resultant was concentrated under reduced pressure to remove the solvent. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (4 g, 0% to 10% MeOH / DCM) to give Z58-b (40 mg, 74.69 pmol, 12.37% yield) as a light yellow solid. MS m / z (ESI): 536.3 [M+H]+. Step 3: Z58-b (40 mg, 74.69 amoi) was dissolved in DCM (3 mL). TFA (1 mL) was added. The mixture was stirred at room temperature for 1 hour. The resultant was concentrated under reduced pressure to remove the solvent and to give crude product Z58 (30 mg, 68.89 Limol, 92.24% yield) as a light yellow solid. It was used directly in the next step without purification. MS m / z (ESI): 436.2 [M+H]+. Preparation of Intermediate Z61 Pd(dppf)CI2,K2CO3 Dioxane / H20,100°C,6hs Z61 Intermediate Z61 was obtained referring to the preparation method of Z49. MS m / z (ESI): 424.1 [M+H]+. Preparation of Intermediate Z62 HCI \ Z62-b HN-0 Step 1: 5-Bromo-6-methylpicolinic acid (2 g, 9.26 mmol) and dimethylhydroxylamine hydrochloride (993.35 mg, 10.18 mmol, HCl) were dissolved in THF (30 mL). TEA (3.75 g, 37.03 mmol, 5.16 mL) and HATU (4.19 g, 11.11 mmol) were added, and the mixture was stirred at room temperature for 2 hours. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (20 g, 0% to 30% EA / PE) to give Z62-a (2.2 g, 8.49 mmol, 91.72% yield) as a light yellow oil. MS m / z (ESI): 259.0 [M+H]+. Step 2: Z62-a (2.2 g, 8.49 mmol) and bis(pinacolato)diboron (3.23 g, 12.74 mmol) were dissolved in dioxane (30 mL). Under argon protection, potassium acetate (2.50 g, 25.47 mmol) and Pd(dppf)Cl2 (621.29 mg, 849.09 gmol) were added. The temperature was raised to 95°C and stirred overnight. The solid was filtered off, and the filtrate was concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (20 g, 0% to 30% EA / PE) to give Z62-b (2.4 g, 7.84 mmol, 92.32% yield) as a light yellow solid. MS m / z (ESI): 307.2 [M+H]+. Step 3:    8-Bromo-1-chloro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c] pyrimidin-5-amine (0.5 g, 1.26 mmol) and Z62-b (577.48 mg, 1.89 mmol) were dissolved in dioxane (10 mL) and water (2 mL). Under argon protection, K2CO3 (347.57 mg, 2.51 mmol) and Pd(dppf)Cl2 (92.01 mg, 125.75 pmol) were added. The temperature was raised to 100°C and stirred for 3 hours. Water and ethyl acetate were added, and extraction was performed three times with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (12 g, 0% to 30% EA / PE) to give Z62-c (0.4 g, 804.96 pmol, 64.01% yield) as a light yellow solid. MS m / z (ESI): 497.2 [M+H]+. Step 4: Z62-c (0.3 g, 603.72 pmol) was dissolved in THF (10 mL). Under argon protection, the temperature was lowered to -78°C, and DIBAL-H (1 M, 2.41 mL) was slowly added dropwise. The mixture was stirred at low temperature for 3 hours. Saturated aqueous ammonium chloride solution was added dropwise at low temperature to quench the reaction. A large amount of anhydrous sodium sulfate and ethyl acetate were added. The solid was filtered off, and the mother liquor was concentrated under reduced pressure to give a crude product. The residue was separated by CombiFlash column chromatography (4 g, 0% to 60% EA / PE) to give Z62 (0.2 g, 456.77 pmol, 75.66% yield) as a light yellow solid. MS m / z (ESI): 438.1 [M+H]+. Preparation of Intermediate Z63 Z63 Intermediate Z63 was prepared referring to step 2 of Z47. MS m / z (ESI): 438.1 [M+H]+. Preparation of Intermediate Z64 Step 1: Under argon protection, 8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine (1 g, 2.75 mmol) was dissolved in THF (50 mL), and n-BuLi (2.5 M, 5.49 mL) was added dropwise at -78°C. After reaction at -78°C for 1 hour, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was slowly added dropwise, and the mixture was reacted at -78°C for 1 hour. The reaction solution was quenched with saturated ammonium chloride solution, stirred at room temperature for 0.5 hour, and then extracted twice with ethyl acetate, and dried by rotary evaporation to give a crude product. The crude product was purified by prep-HPLC to give Z64-a (200 mg, 486.34 pmol, yield 17.71%) as a white solid. MS m / z (ESI): 330.1 [M+H]+. Step 2:   6-Bromo-3-iodo-2-methylpyridine (1 g, 3.36 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (1.04 g, 3.36 mmol) were dissolved in 1,4-dioxane (20 mL), water (4 mL), and DMSO (2 mL). Pd(dppf)Cl2 (245.60 mg, 335.66 pmol) and K2CO3 (927.84 mg, 6.71 mmol) were then added. The mixture was stirred at 65°C for 3 hours. The reaction solution was concentrated, water and ethyl acetate were then added.The mixture was extracted with ethyl acetate, washed three times with saturated brine, dried, filtered, and concentrated. The resultant was purified by CombiFlash column chromatography (petroleum ether:ethyl acetate = 70%:30%) to give Z64-b (1.2 g, 3.16 mmol, yield 94.20%) as a colorless oil. MS m / z (ESI): 353.1 [M+H]+. Step 3: Under argon protection, Z64-b (153.50 mg, 434.53 pmol), Z64-a (110 mg, 334.25 pmol), Pd(dppf)Cl2 (43.17 mg, 66.85 pmol), K2CO3 (115.49 mg, 835.63 pmol), 1,4-dioxane (10 mL), and water (0.5 mL) were mixed and heated to 100°C, and the mixture was reacted for 3 hours. Water and ethyl acetate were added to the reaction solution, the organic layer was separated, washed with saturated brine, and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 20%:80%) to give Z64-c (170 mg, 304.87 pmol, yield 91.21%) as a yellow oil. MS m / z (ESI): 558.3 [M+H]+. Step 4: Under hydrogen atmosphere, Z64-c (70 mg, 125.53 pmol), platinum dioxide (2.85 mg, 12.55 pmol), methanol (2 mL), and EA (2 mL) were stirred at room temperature for 6 hours. The reaction solution was filtered and concentrated to give Z64-d (70 mg, 125.08 pmol, yield 99.64%) as a yellow solid oil. The crude product was used directly in the next step. MS m / z (ESI): 560.3 [M+H]+. Step 5: At room temperature, Z64-d (70 mg, 125.08 pmol), TFA (1 mL), and DCM (1 mL) were stirred for 1 hour. The reaction solution was concentrated to give a crude product. The crude product was dissolved in dichloromethane, saturated sodium bicarbonate was added to adjust the pH to 9-10, then the mixture was extracted with dichloromethane:methanol = 10:1 (10 mL*2). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated to give Z64 (50 mg, 108.81 pmol, yield 86.99%) as a yellow solid. MS m / z (ESI): 460.2 [M+H]+. Preparation of Intermediate Z65 Intermediate Z65 was prepared according to the above synthetic route and by reference to the preparation method of Z56. MS m / z (ESI): 492.2 [M+H]+. Preparation of Intermediate Z66 Z66-a Z66 Step 1: Z66-a (200 mg, 401.36 pmol) was dissolved in DMF (4 mL). Trimethylcyclotriboroxane (3.5 M, 1 mL), K2CO3 (443.76 mg, 3.21 mmol), and Pd(dppf)Cl2 (88.10 mg, 120.41 pmol) were then added. The mixture was stirred under microwave at 120°C for 3 hours. After the reaction was complete, the solvent was dried by rotary evaporation under reduced pressure, and the residue was separated by 10 CombiFlash (12 g, 0-100% DCM / EA) to successfully give product Z66-b (127 mg, 293.01 pmol, 73.00% yield) as a light yellow solid. MS m / z (ESI): 434.1 [M+H]+. Step 2: Z66-b (127 mg, 293.01 pmol) was dissolved in THF (6 mL) and water (2 mL). LiOH (70.17 mg, 2.93 mmol) was then added. The mixture was stirred at room temperature for 2 hours, then neutralized with dilute hydrochloric acid (2N), filtered, and the solid was dried under vacuum to 15 successfully give product Z66 (87 mg, 207.44 pmol, 70.79% yield) as a yellow solid. MS m / z (ESI): 420.2 [M+H]+. Preparation of Intermediate Z67 Step 1: 4-((tert-Butoxycarbonyl)amino)butanoic acid (502.84 mg, 2.47 mmol) and (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)et hyl)pyrrolidine-2-carboxamide (1 g, 2.25 mmol) were dissolved in DMF (25 mL). DIPEA (872.09 mg, 6.75 mmol, 1.18 mL) and HATU (1.27 g, 3.37 mmol) were then added. The mixture was stirred at room temperature for 1 hour. The reaction solution was then dried by rotary evaporation under reduced pressure and purified by column chromatography CombiFlash (24 g, 0-10% MeOH / DCM) to successfully give product Z67-a (0.8 g, 1.27 mmol, 56.47% yield) as a light yellow solid. MS m / z (ESI): 530.3 [M-100+H]+. Step 2: Z67-a (0.8 g, 1.27 mmol) was dissolved in DCM (20 mL). HCl (4 M in EA, 5 mL) was then added. The mixture was stirred at room temperature for 1 hour. The reaction solution was then concentrated to give product Z67-b (719 mg, 1.27 mmol, 99.98% yield, HCl) as a yellow solid. MS m / z (ESI): 530.3 [M+H]+. Step 3: 5-Bromo-4-chloro-2-(methylthio)pyrimidine (9.66 g, 43.84 mmol) was dissolved in DMF (120 mL). The temperature was lowered to 0°C, and then NaH (3.19 g, 83.34 mmol, 60% purity) was added portionwise. The mixture was stirred at 0°C for 1 hour. Then a solution of 5-bromo-4-chloro-2-(methylamino)pyrimidine (10 g, 41.75 mmol) in DMF (120 mL) was added dropwise to the reaction solution. After the addition, the mixture was warmed to room temperature and stirred for 2 hours. After the reaction was complete, the mixture was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate (250 mL'3), washed with water (100 mL*3), washed with saturated brine (100 mL*2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was dried by rotary evaporation under reduced pressure to give crude product Z67-c (15 g, 35.43 mmol, 84.87% yield) as an oil. MS m / z (ESI): 423.0 [M+H]+. Step 4: At 0°C, aqueous HCl (3 M, 30 mL) was added to a solution of Z67-c (15 g, 35.43 mmol) in THF (200 mL). The reaction solution was stirred at room temperature for 1 hour. The reaction solution was then concentrated, basified to pH 8-9 with aqueous Na2CO3 solution, extracted with DCM (500 mL*2), washed with saturated brine (100 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to successfully give product Z67-d (8.5 g, 32.80 mmol, 92.57% yield) as a red oil. MS m / z (ESI): 259.0 [M+H]+. Step 5: A mixture of formic acid (39 g, 720.26 mmol, 31.97 mL, 85% purity) and acetic anhydride (34.8 g, 328.21 mmol, 32.01 mL) was heated at 50°C for 1 hour. The reaction mixture was then cooled to room temperature and added to a solution of Z67-d (8.5 g, 32.80 mmol) in DCM (100 mL). The reaction solution was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was concentrated, water (500 mL) was added, and the mixture was extracted with DCM (500 mL*3). The organic phases were combined, washed sequentially with water (200 mL) and brine (100 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to successfully give product Z67-e (8.5 g, 29.60 mmol, 90.25% yield) as a light yellow solid. MS m / z (ESI): 287.0 [M+H]+. Step 6: POCl3 (9.05 g, 50.18 mmol, 7.42 mL, 85% purity) was added dropwise to a solution of Z67-e (8.5 g, 29.60 mmol) in dioxane (83.96 mL). The reaction mixture was then heated to reflux for 4 hours. The reaction solution was cooled to room temperature and concentrated, diluted with DCM (100 mL), and adjusted to pH = 8 with saturated aqueous NaHCO3 solution. The mixture was extracted with DCM (200 mL*3). The organic phases were combined, washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The resultant was purified by CombiFlash (40 g, 0-100% PE / EA) successfully to give product Z67-f (6.5 g, 24.15 mmol, 81.59% yield) as a light yellow solid. MS m / z (ESI): 269.0 [M+H]+. Step 7: At 0°C, Z67-f (1.6 g, 5.95 mmol) was dissolved in DCM (35 mL). m-CPBA (3.73 g, 18.39 mmol, 85% purity) was then added. The mixture was allowed to warm to room temperature and stirred for 18 hours. Then (5-fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (1.19 g, 7.13 mmol) and sodium carbonate (3.14 g, 29.60 mmol) were added, and the mixture was stirred at room temperature for 4 hours. After the reaction was complete, the reaction solution was filtered, and the filtrate was dried by rotary evaporation under reduced pressure. The resultant was purified by CombiFlash (12 g, 0-60% DCM / MeOH) successfully to give product Z67-g (600 mg, 1.55 mmol, 26.00% yield) as a light yellow solid. MS m / z (ESI): 388.0 [M+H]+. Step 8: Z67-g (225 mg, 579.61 gmol) and (6-methoxycarbonyl-3-pyridyl)boronic acid (209.76 mg, 1.16 mmol) were dissolved in dioxane (10 mL) and water (3 mL). K2CO3 (400.53 mg, 2.90 mmol) and Pd(dppf)Cl2 (127.23 mg, 173.88 pmol) were then added. The mixture was stirred at 105°C for 2 hours. After the reaction was complete, the mixture was extracted twice with water (25 mL*2). The aqueous phases were combined, neutralized with HCl (2N), and the precipitated solid was filtered out and dried under vacuum to successfully give product Z67 (170 mg, 394.99 pmol, 68.15% yield) as a brown solid. MS m / z (ESI): 431.1 [M+H]+. Preparation of Intermediate Z68 Z68 Step 1: 8-Bromo-N-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl]imidazo[1,5-c]pyrimidin-5-amine (300 mg, 0.83 mmol) and methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate (652 mg, 2.48 mmol) were dissolved in 1,4-dioxane (20 mL) and water (3 mL). Tetrakis(triphenylphosphine)palladium(0) (191 mg, 0.16 mmol) and potassium carbonate (228 mg, 1.65 mmol) were added. The reaction solution was stirred at 100°C for 20 hours. The solvent was concentrated under reduced pressure, and the crude product was separated by CombiFlash (0-10% MeOH / DCM) to give product methyl 5-[5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino] imidazo[1,5-c]pyrimidin-8-yl]pyridine-2-carboxylate (340 mg, 98.14% yield) as a yellow solid. MS m / z (ESI): 420.1 [M+H]+. Step 2:   Methyl 5-[5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]imidazo[1,5-c] pyrimidin-8-yl]pyridine-2-carboxylate (323 mg, 0.77 mmol) was dissolved in tetrahydrofuran (10 mL), cooled to 0°C, and N-iodosuccinimide (173 mg, 0.77 mmol) was added. The reaction solution was stirred at 0°C for 1 hour. The reaction solution was poured into water, extracted with DCM (100 mL*3), dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure. The obtained crude product was separated by CombiFlash (0-10% MeOH / DCM) to give product methyl 5-[5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-1-iodoimidazo[1,5-c]pyrimidin-8-yl]pyridine-2-carboxylate (350 mg, 83.34% yield) as a yellow solid. MS m / z (ESI): 546.1 [M+H]+. Step 3: Methyl 5-[5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-1-iodoimidazo[1,5-c] pyrimidin-8-yl]pyridine-2-carboxylate (350 mg, 0.64 mmol) was dissolved in DMF (15 mL). CuI (1.22 g, 6.42 mmol), PdCl2(dppf) (47 mg, 0.064 mmol), and methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (1.23 g, 6.42 mmol) were added. The reaction solution was stirred at 90°C overnight under argon protection. The reaction solution was filtered, washed, and the solvent was concentrated under reduced pressure. The obtained crude product was separated by CombiFlash (0-10% MeOH / DCM) to give product methyl 5-[5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-1-(trifluoromethyl)imidazo [1,5-c]pyrimidin-8-yl]pyridine-2-carboxylate (200 mg, 63.93% yield) as a yellow solid. MS m / z (ESI): 488.1 [M+H]+. Step 4: Methyl 5-[5-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-1-(trifluoromethyl) imidazo[1,5-c]pyrimidin-8-yl]pyridine-2-carboxylate (100 mg, 0.21 mmol) was dissolved in tetrahydrofuran (15 mL), and potassium trimethylsilanolate (40 mg, 0.31 mmol) was added. The reaction solution was stirred at room temperature for 4 hours. The reaction solution was separated by CombiFlash (0-80% MeOH / DCM) to give product Z68 (50 mg, 51.48% yield) as a yellow solid. MS m / z (ESI): 474.1 [M+H]+. Preparation of Intermediate H159-b H159-a H159-b Step 1: Compound 8-bromo-1-fluoro-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo [1,5-c]pyrimidin-5-amine         (760         mg,         2         mmol),         tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (754 mg, 2 mmol), potassium carbonate (828 mg,    6 mmol),    and catalyst [1,1'-bis(diphenylphosphinoferrocene]dichloropalladium(II) (146 mg, 0.2 mmol) were added to a mixed solvent of 5 ml of 1,4-dioxane and 1 ml of water. The mixture was purged with nitrogen three times, the mixture was heated to 100°C and stirred for 5 hours. After the reaction was complete, silica gel was directly added to the mixture for sample loading, and the resultant was purified by column chromatography using 30-100% PE / EA. The target product was concentrated to give compound H159-a (552 mg, 1 mmol). Yield: 50%. MS m / z (ESI): 552 [M+H]+. Step 2: Compound H159-a (552 mg, 1 mmol) was added to a mixed solvent of 5 ml of dichloromethane and 1 ml of trifluoroacetic acid, the mixture was stirred at room temperature for 1 hour, and then concentrated and dried under oil pump vacuum to give compound H159-b (451 mg, 1 mmol). Yield: 100%. MS m / z (ESI): 452 [M+H]+. Preparation of Intermediate H80-d Step 1: Under argon protection, 1-bromo-4-iodobenzene (8.20 g, 28.98 mmol), methyl 3-aminocyclobutanecarboxylate hydrochloride (4 g, 24.15 mmol), L-proline (1.11 g, 9.66 mmol), copper(I) iodide (919.95 mg, 4.83 mmol), potassium carbonate (6.68 g, 48.30 mmol), and DMSO (40 mL) were mixed and heated to 80°C, and the mixture was reacted for 16 hours. The reaction solution was poured into water, extracted with ethyl acetate (20 mL*2), and the organic layers were combined, washed and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 80%:20%) to give H80-a (4.6 g, 16.19 mmol, yield 67.03%) as a yellow solid. MS m / z (ESI): 284.1 [M+H]+. Step 2:    Under argon protection, H80-a    (730 mg, 2.01 mmol), 8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine  (628.25 mg, 2.21 mmol), palladium acetate (90.25 mg, 402.00 pmol), n-butyldi(1-adamantyl)phosphine (144.13 mg, 402.00 pmol), potassium carbonate (1.11 g, 8.04 mmol), bis(pinacolato)diboron (1.02 g, 4.02 mmol), DME (20 mL), and water (2 mL) were mixed and heated to 70°C, and the mixture was reacted for 16 hours. The reaction solution was filtered, and the filtrate was extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 20%:80%) to give H80-b (540 mg, 1.11 mmol, yield 55.11%) as a yellow solid. MS m / z (ESI): 488.3 [M+H]+. Step 3: H80-b (490 mg, 804.06 pmol), THF (20 mL), and TFA (2 mL) were mixed and stirred at room temperature for 5 minutes, then cooled to -15°C, and N-iodosuccinimide (180.90 mg, 804.06 pmol) was added. After addition, the mixture was reacted at -15°C for 15 minutes. The reaction solution was poured into ice water, saturated sodium bicarbonate solution was added to adjust the pH > 7, and then the mixture was extracted with ethyl acetate (10 mL*2). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 50%:50%) to give H80-c (55 mg, 89.66 pmol, yield 11.15%) as a yellow solid. MS m / z (ESI): 614.1 [M+H]+. Step 4: At room temperature, lithium hydroxide (5.86 mg, 244.53 pmol) was added to a solution of H80-c (50 mg, 81.51 pmol) in THF (2 mL) and water (0.5 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was concentrated, 1N HCl was added to adjust the pH < 3, and the aqueous phase was lyophilized to give H80-d (48 mg, 80.08 pmol, yield 98.25%) as a white solid. MS m / z (ESI): 600.2 [M+H]+. Preparation of Intermediate H87-h Step 1: Under argon protection, 1-bromo-4-iodobenzene (13.33 g, 47.10 mmol), 4-(dimethoxymethyl)piperidine (5 g, 31.40 mmol), L-proline (1.45 g, 12.56 mmol), copper(I) iodide (1.20 g, 6.28 mmol), potassium carbonate (8.68 g, 62.80 mmol), and DMSO (50 mL) were mixed and heated to 80°C, and the mixture was reacted for 16 hours. The reaction solution was filtered, and the filtrate was added to water, extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed three times with water and once with saturated brine, then concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 70%:30%) to give H87-a (6.1 g, 19.41 mmol, yield 61.82%) as a yellow solid. MS m / z (ESI): 314.1 [M+H]+. Step 2: At room temperature, TFA (5 mL) was added to a solution of H87-a (6.1 g, 19.41 mmol) in DCM (10 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was concentrated to give a crude product. The crude product was dissolved in dichloromethane, washed once with saturated sodium bicarbonate solution, washed once with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give H87-b (5 g, 18.65 mmol, yield 96.05%) as a yellow liquid. The crude product was used directly in the next step. MS m / z (ESI): 268.1 [M+H]+. Step 3: NaBH(OAc)3 (13.66 g, 64.43 mmol) was added to a solution of tert-butyl piperazine-1-carboxylate (3 g, 16.11 mmol), H87-b (4.75 g, 17.72 mmol), DCM (50 mL), and AcOH (0.5 mL). After addition, the mixture was reacted at room temperature for 3 hours. The reaction solution was poured into water, extracted with dichloromethane (10 mL*2). The organic layers were combined, washed with saturated brine and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 80%:20%) to give H87-c (4.8 g, 10.95 mmol, yield 67.97%) as a yellow solid. MS m / z (ESI): 438.0 [M+H]+. Step 4: At room temperature, TFA (10 mL) was added to a solution of H87-c (4.8 g, 10.95 mmol) in DCM (20 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was concentrated, dichloromethane was added, saturated sodium bicarbonate solution was added to adjust the pH > 8.The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated to give H87-d (4 g, 8.84 mmol, 80.77% yield, TFA) as a yellow solid. The crude product was used directly in the next step. MS m / z (ESI): 338.2 [M+H]+. Step 5: H87-d (4 g, 8.84 mmol), methyl 3-methyl-2-(3-(((perfluorobutyl)sulfonyl)oxy)isoxazol-5-yl)butanoate (6.38 g, 13.27 mmol), DIPEA (3.43 g, 26.53 mmol, 4.62 mL), and DMSO (50 mL) were mixed and heated to 110°C, and the mixture was reacted for 16 hours. The reaction solution was poured into ice water, and extracted with ethyl acetate (30 mL*2). The organic layers were combined, washed three times with water, once with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by column chromatography (dichloromethane:ammonia / methanol = 95%:5%) to give H87-e (4.3 g, 8.28 mmol, yield 93.60%) as a brown liquid. MS m / z (ESI): 519.2 [M+H]+. Step 6: H87-e (1 g, 1.93 mmol) and bis(pinacolato)diboron (1.47 g, 5.78 mmol) were dissolved in 1,4-dioxane (20 mL). Under argon protection, Pd(dba)2 (218.28 mg, 385.01 pmol) and PCy3 (259.12 mg, 924.01 pmol) were added, and the mixture was heated to 120°C and stirred for 24 hours. The reaction solution was filtered, and the filtrate was concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether / triethylamine:dichloromethane = 85%:15%) to give H87-f (700 mg, 1.24 mmol, yield 64.18%) as a yellow solid. MS m / z (ESI): 567.4 [M+H]+. Step 7: Under argon protection, 8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine (400 mg, 1.10 mmol), H87-f (684.50 mg, 1.21 mmol), [1,1'-bis(diphenylphosphinoferrocene]dichloropalladium(II) (80.37 mg, 109.84 pmol), potassium carbonate (455.41 mg, 3.30 mmol), 1,4-dioxane (20 mL), and DMSO (1 mL) were mixed and heated to 100°C, and the mixture was reacted for 2 hours. The reaction solution was filtered, ethyl acetate and saturated brine were added to the filtrate, the organic layer was separated, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate / triethylamine = 80%:20% to 0:100%) to give H87-g (470 mg, 649.32 pmol, yield 59.12%) as a yellow solid. MS m / z (ESI): 724.4 [M+H]+. Step 8: At room temperature, LiOH (76.10 mg, 3.18 mmol) was added to a solution of H87-g (460 mg, 635.50 pmol) in THF (6 mL), methanol (4 mL), and water (2 mL). After addition, the mixture was reacted at room temperature for 1 hour. The pH of the reaction solution was adjusted to 5-6 with 1N aqueous HCl solution. After adding ethyl acetate, a large amount of yellow solid precipitated. The solid was collected and dried to give H87-h (400 mg, 563.53 pmol, yield 88.67%) as a yellow solid. MS m / z (ESI): 710.4 [M+H]+. Preparation of Intermediates H66-b and H86-b H86-a H66-a Step 1:    Ethyl    1-(4-(5-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino)imidazo[1,5- c]pyrimidin-8-yl)phenyl)azetidine-3-carboxylate (700 mg, 1.44 mmol) was dissolved in THF (10 mL). The temperature was lowered to 0°C, and N-iodosuccinimide (226.13 mg, 1.01 mmol) was then added. The mixture was stirred at 0°C for 0.5 hour. Saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate (70 mL*3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to give a crude product. The resultant was purified by CombiFlash (12 g, 0-50% EA / PE) successfully to give a mixture of H86-a and H66-a (88 mg, 143.46 pmol, 9.99% yield) as a light yellow solid. MS m / z (ESI): 614.2 [M+H]+. Step 2: The mixture of H86-a and H66-a (80 mg, 130.42 pmol) was dissolved in THF (8 mL) and water (2 mL). LiOH (62.46 mg, 2.61 mmol) was then added. The mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was neutralized to pH=3-4 with dilute hydrochloric acid (2N), and then the solvent was dried by rotary evaporation under reduced pressure to successfully give a mixture of H86-b and H66-b (66 mg, 112.75 pmol, 86.45% yield) as a white solid. MS m / z (ESI): 586.1 [M+H]+. Preparation of Intermediate H64-b Step 1: Dibromohydroxycarbonate (25 g, 123.25 mmol) was dissolved in EA (250 mL) and water (25 mL). 3-Butyn-1-ol (34.56 g, 493.02 mmol) and NaHCO3 (31.80 g, 369.76 mmol) were added, and the mixture was reacted at room temperature for 3 hours. The reaction solution was filtered, water was added to the filtrate, the layers were separated, and the mixture was extracted twice with ethyl acetate. The organic phase was washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and dried by rotary evaporation to give a crude product. The crude product was purified by column chromatography (petroleum ether:dichloromethane =  50%:50% to 0:100%) to give 2-(3-bromoisoxazol-5-yl)ethan-1-ol (18 g, 93.74 mmol, yield 76.06%) as a yellow liquid. MS m / z (ESI): 192.0 [M+H]+. Step 2: At 0°C, 2-(3-bromoisoxazol-5-yl)ethan-1-ol (18 g, 93.74 mmol) was dissolved in acetone (150 mL). Jones reagent (100 mL) was added, and the mixture was reacted at room temperature for 16 hours. The reaction solution was slowly poured into ice water, extracted twice with ethyl acetate. The organic phases were combined, washed twice with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give 2-(3-bromoisoxazol-5-yl)acetic acid (16.8 g, 81.56 mmol, yield 87.00%) as a brown liquid. The crude product was used directly in the next step. MS m / z (ESI): 203.7 [M+H]+. Step 3: 2-(3-Bromoisoxazol-5-yl)acetic acid (16 g, 77.67 mmol) was dissolved in methanol (100 mL). Concentrated sulfuric acid (2 mL) was added, and the mixture was reacted at 70°C for 1 hour. The reaction solution was concentrated to a smaller volume, water was added, the mixture was extracted with dichloromethane (50 mLx2), washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:dichloromethane =   30%:70%) to give methyl 2-(3-bromoisoxazol-5-yl)acetate (14 g, 63.63 mmol, yield 81.92%) as a white solid. MS m / z (ESI): 220.0 [M+H]+. Step 4: Methyl 2-(3-bromoisoxazol-5-yl)acetate (14 g, 63.63 mmol) was dissolved in THF (150 mL). Under ice bath cooling, potassium tert-butoxide (10.69 g, 95.27 mmol) was added, stirred for 10 min, and 2-iodopropane (14.06 g, 82.72 mmol, 8.26 mL) was slowly added dropwise. After addition, the mixture was reacted at room temperature for 16 hours. The reaction solution was poured into ice water, extracted twice with ethyl acetate, washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and dried by rotary evaporation to give crude methyl 2-(3-bromoisoxazol-5-yl)-3-methylbutanoate (8 g, 30.52 mmol, yield 47.97%) as a yellow oil. The crude product was used directly in the next step. MS m / z (ESI): 262.0 [M+H]+. Step 5: Methyl 2-(3-bromoisoxazol-5-yl)-3-methylbutanoate (8 g, 30.52 mmol), potassium hydroxide (8.56 g, 152.61 mmol), methanol (45 mL), and water (5 mL) were added to a pressure vessel and reacted at 110°C for 16 hours. The reaction solution was filtered, the filtrate was concentrated, ice water was added, and the mixture was washed once with ethyl acetate. The aqueous phase was collected, adjusted to pH < 4 with concentrated hydrochloric acid at 0°C, and then extracted with ethyl acetate (50 mL*2). The organic layers were combined, washed with saturated brine, dried over      anhydrous       sodium       sulfate,       and      concentrated      to       give 2-(3-methoxyisoxazol-5-yl)-3-methylbutanoic acid (5.1 g, 25.60 mmol, yield 83.88%) as a yellow liquid. The crude product was used directly in the next step. MS m / z (ESI): 200.2 [M+H]+. Step 6: 2-(3-Methoxyisoxazol-5-yl)-3-methylbutanoic acid (5 g, 25.10 mmol) and HBr / AcOH (20 mL) were heated to 80°C and reacted for 0.5 hour. The reaction solution was concentrated to give 2-(3-hydroxyisoxazol-5-yl)-3-methylbutanoic acid (4.6 g, 24.84 mmol, yield 98.97%) as a yellow liquid. The crude product was used directly in the next step. MS m / z (ESI): 186.1 [M+H]+. Step 7: Thionyl chloride (13.30 g, 111.78 mmol, 8.12 mL) was added dropwise to a solution of 2-(3-hydroxyisoxazol-5-yl)-3-methylbutanoic acid (4.6 g, 24.84 mmol) in methanol (50 mL). After addition, the mixture was reacted at room temperature for 2 hours. The reaction solution was concentrated to dryness, water was added, and the mixture was extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed with saturated brine and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:dichloromethane = 50%:50%) to give methyl 2-(3-hydroxyisoxazol-5-yl)-3-methylbutanoate (3.8 g, 19.08 mmol, yield 76.79%) as a brown-red liquid. MS m / z (ESI): 200.1 [M+H]+. Step 8: Methyl 2-(3-hydroxyisoxazol-5-yl)-3-methylbutanoate (3.8 g, 19.08 mmol), potassium carbonate (5.27 g, 38.15 mmol), and acetonitrile (100 mL) were mixed, and perfluorobutanesulfonyl fluoride (6.63 g, 21.94 mmol) was added dropwise. After addition, the mixture was reacted at room temperature for 2 hours. The reaction solution was filtered, and the filtrate was concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:dichloromethane = 80%:20%) to give methyl 3-methyl-2-(3-(((perfluorobutyl)sulfonyl)oxy) isoxazol-5-yl)butanoate (3 g, 6.23 mmol, yield 32.68%) as a colorless liquid. MS m / z (ESI): 482.0 [M+H]+. Step 9: Under argon protection, 1-bromo-4-iodobenzene (7.29 g, 25.77 mmol), tert-butyl piperazine-1-carboxylate (4 g, 21.48 mmol, HCl), L-proline (989.03 mg, 8.59 mmol), copper(I) iodide (818.04 mg, 4.30 mmol), potassium carbonate (5.94 g, 42.95 mmol), and DMSO (40 mL) were mixed and heated to 80°C, and the mixture was reacted for 16 hours. The reaction solution was poured into water, extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 80%:20%) to give tert-butyl 4-(4-bromophenyl)piperazine-1- carboxylate (3 g, 8.79 mmol, yield 40.94%) as a yellow solid. MS m / z (ESI): 285.1 [M+H-56]+. Step 10: At room temperature, TFA (2.5 mL) was added to a solution of tert-butyl 4-(4-bromophenyl)piperazine-1-carboxylate (1 g, 2.93 mmol) in DCM (5 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was concentrated to dryness to give 1-(4-bromophenyl)piperazine (700 mg, 2.90 mmol, 99.06% yield) as a yellow solid. The crude product was used directly in the next step. MS m / z (ESI): 241.1 [M+H]+. Step 11:    1-(4-Bromophenyl)piperazine (500 mg, 2.07 mmol), methyl 3-methyl-2-(3-(((perfluorobutyl)sulfonyl)oxy)isoxazol-5-yl)butanoate (798.40 mg, 1.66 mmol), DIPEA (803.99 mg, 6.22 mmol, 1.08 mL), and DMSO (15 mL) were heated to 110°C, and the mixture was reacted for 16 hours. The reaction solution was poured into ice water, extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed three times with water, once with saturated brine, and concentrated to give a crude product. The crude product was purified by column chromatography (dichloromethane:ammonia / methanol 4M =  98%:2%) to give methyl 2-(3-(4-(4-bromophenyl)piperazin-1-yl)isoxazol-5-yl)-3-methylbutanoate (268 mg, 634.60 pmol, yield 30.60%) as a brown oil. MS m / z (ESI): 422.1 [M+H]+. Step 12: Under argon protection, methyl 2-(3-(4-(4-bromophenyl)piperazin-1-yl)isoxazol-5-yl)-3-methylbutanoate (255.12 mg, 604.11 pmol), 8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine (200 mg, 549.19 pmol), palladium acetate (24.66 mg, 109.84 umol), n-butyldi(1-adamantyl)phosphine (39.38 mg, 109.84 pmol), potassium carbonate (303.60 mg, 2.20 mmol), bis(pinacolato)diboron (278.92 mg, 1.10 mmol), DME (25 mL), and water (5 mL) were heated to 85°C, and the mixture was reacted for 16 hours. The reaction solution was filtered, the filtrate was concentrated, water was added, the mixture was extracted with ethyl acetate (10 mL*2), the organic layers were combined, washed with saturated brine, and concentrated to give a crude product. The crude product was purified by column chromatography (dichloromethane:ammonia / methanol 4M = 95%:5%) to give H64-a (150 mg, 239.36 pmol, 43.58% yield) as a brown oil. MS m / z (ESI): 627.3 [M+H]+. Step 13: At room temperature, lithium hydroxide (9.36 mg, 390.95 pmol) was added to a solution of H64-a (140 mg, 78.19 pmol) in THF (2 mL), methanol (2 mL), and water (1 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was concentrated, washed once with ethyl acetate, then adjusted to pH=6-7 with 1N HCl, extracted with ethyl acetate (5 mL*2), and the organic layers were combined, dried over anhydrous sodium sulfate and concentrated to give H64-b (45 mg, 73.45 pmol, yield 93.94%) as a yellow oil. MS m / z (ESI): 613.3 [M+H]+. Preparation of Intermediate H64-f Step 1: Under argon protection, tert-butyl (S)-(1-(4-bromophenyl)ethyl)carbamate (5 g, 16.66 mmol), 4-methylthiazole (3.30 g, 33.31 mmol), palladium acetate (37.39 mg, 166.56 pmol), potassium acetate (3.27 g, 33.31 mmol), and DMA (10 mL) were mixed and heated to 150°C, and the mixture was reacted for 4 hours. The reaction solution was filtered, ice water was added to the filtrate, and the mixture was extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed three times with water, once with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 75%:25%) to give H64-c (5.2 g, 16.33 mmol, yield 98.04%) as a yellow solid. MS m / z (ESI): 319.1 [M+H]+. Step 2: At room temperature, HCl / 1,4-dioxane (15 mL) was added to a solution of H64-c (5.1 g, 16.02 mmol) in DCM (30 mL). After addition, the mixture was reacted at room temperature for 2 hours. The reaction solution was filtered, and the solid was collected to give H64-d (4 g, 15.70 mmol, 98.03% yield, HCl) as a yellow solid. MS m / z (ESI): 219.1 [M+H]+. Step 3: At room temperature, H64-d (4.34 g, 18.76 mmol), HATU (7.81 g, 20.54 mmol), DIPEA (6.93 g, 53.59 mmol, 9.33 mL), and DMF (50 mL) were mixed, and rac-(1S)-1-[4-(4-methylthiazol-5-yl)phenyl]ethanamine (3.9 g, 17.86 mmol) was added. After addition, the mixture was reacted at room temperature for 2 hours. The reaction solution was poured into water, and the aqueous phase was extracted with ethyl acetate (20 mL*2). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated to give a crude product. The crude product was purified by column chromatography (dichloromethane:methanol = 95%:5%) to give H64-e (6 g, 13.90 mmol, yield 77.83%) as a white solid. MS m / z (ESI): 432.2 [M+H]+. Step 4: H64-e (1 g, 2.32 mmol) was dissolved in HCl / 1,4-dioxane (4 M) (20 mL) and stirred at room temperature for 2 hours. The solvent was concentrated under reduced pressure to give crude product H64-f (720 mg, 2.17 mmol, 93.75% yield) as a pink solid. The crude product was used directly in the next step. MS m / z (ESI): 332.2 [M+H]+. Preparation of Intermediate H65-g Step 1: Under argon protection, 1-bromo-4-iodobenzene (6.40 g, 22.61 mmol), 4-(dimethoxymethyl)piperidine (3 g, 18.84 mmol, HCl), L-proline (867.68 mg, 7.54 mmol), copper(I) iodide (717.66 mg, 3.77 mmol), potassium carbonate (5.21 g, 37.68 mmol), and DMSO (40 mL) were mixed and heated to 80°C, and the mixture was reacted for 16 hours. The reaction solution was poured into water, extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed with saturated brine and concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 100% to 80%:20%) to give H65-a (3.2 g, 10.18 mmol, yield 54.05%) as a yellow solid. MS m / z (ESI): 314.1 [M+H]+. Step                2:                Under                argon                protection, 8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine (500 mg, 1.37 mmol), H65-a (474.55 mg, 1.51 mmol), palladium acetate (61.65 mg, 274.60 pmol), n-butyldi(1-adamantyl)phosphine (98.45 mg, 274.60 umol). potassium carbonate (759.01 mg, 5.49 mmol), bis(pinacolato)diboron (697.30 mg, 2.75 mmol), DME (20 mL), and water (2 mL) were mixed and heated to 85°C, and the mixture was reacted for 16 hours. The reaction solution was filtered, the aqueous layer was separated from the filtrate, and the resultant was concentrated to give a crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 50%:50% to 0%:100%) to give H65-b (120 mg, 231.40 umol, yield 16.85%) as a yellow solid. MS m / z (ESI): 519.3 [M+H]+. Step 3: At room temperature, TFA (0.5 mL) was added to a solution of H65-b (50 mg, 96.42 umol) in DCM (1 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was concentrated to give H65-c (36 mg, 76.19 umol, yield 79.02%) as a yellow solid. The crude product was used directly in the next step. MS m / z (ESI): 473.2 [M+H]+. Step 4:   tert-Butyl piperazine-1-carboxylate (400 mg, 2.15 mmol), methyl 3-methyl-2-(3-(((perfluorobutyl)sulfonyl)oxy)isoxazol-5-yl)butanoate (930.27 mg, 1.93 mmol), DIPEA (832.68 mg, 6.44 mmol, 1.12 mL), and DMSO (15 mL) were heated to 110°C, and the mixture was reacted for 16 hours. The reaction solution was poured into ice water, extracted with ethyl acetate (20 mL*2). The organic layers were combined, washed three times with water, once with saturated brine, and concentrated to give a crude product. The crude product was purified by column chromatography (dichloromethane:ammonia / methanol 4M = 95%:5%) to give H65-d (700 mg, 1.91 mmol, yield 88.71%) as a brown oil. MS m / z (ESI): 312.1 [M+H-56]+. Step 5: At room temperature, H65-d (200 mg, 544.31 pmol), NaOH (78.21 mg, 1.96 mmol), THF (6 mL), and water (2 mL) were mixed and stirred for reaction for 16 hours. The reaction solution was concentrated, 1N HCl was added to adjust the pH to 4-5, and then the mixture was extracted with ethyl acetate (5 mL*2). The organic layers were combined, washed with saturated brine and concentrated to give H65-e (90 mg, 254.66 pmol, yield 46.79%) as a brown solid. MS m / z (ESI): 298.1 [M+H-56]+. Step 6: At room temperature, H65-e (80 mg, 226.36 pmol), H64-f (75.02 mg, 226.36 pmol), DIPEA (87.77 mg, 679.09 pmol, 118.29 pL), and DMF (5 mL) were mixed, and HATU (102.48 mg, 271.64 pmol) was added. After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was filtered, ice water was added to the filtrate, and the mixture was extracted with ethyl acetate (15 mL*2). The organic layers were combined, washed with saturated brine and concentrated to give a crude product. The crude product was purified by column chromatography (dichloromethane:ammonia / methanol 4M = 95%:5%) to give H65-f (100 mg, 149.96 pmol, yield 66.25%) as a brown solid. MS m / z (ESI): 611.3 [M+H-56]+. Step 7: At room temperature, TFA (1 mL) was added to a solution of H65-f (90 mg, 134.97 pmol) in DCM (2 mL). After addition, the mixture was reacted at room temperature for 1 hour. The reaction solution was concentrated to dryness, ethyl acetate was added to the residue, saturated sodium bicarbonate solution was added to adjust the pH > 8, the organic layer was separated and concentrated to give H65-g (55 mg, 97.05 pmol, yield 71.91%) as a yellow solid. The crude product was used directly in the next step. MS m / z (ESI): 567.3 [M+H]+. Preparation of Intermediate   8-(5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino) imidazo[1,5-c]pyrimidin-8-yl)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid Step 1: Methyl 5-bromo-6-aminopyridine-2-carboxylate (4.0 g, 17.31 mmol) was dissolved in toluene (40 mL). N,N-Dimethylformamide dimethyl acetal (4.63 mL, 34.62 mmol) was then added. The mixture was stirred at 110°C for 4 hours. The crude reaction solution was concentrated to give crude product methyl (E)-5-bromo-6-((dimethylamino)methylene)amino)picolinate (5.1 g, yellow solid, crude), which was used directly in the next step without purification. MS m / z (ESI): 286.0 [M+H]+. Step 2: Methyl (E)-5-bromo-6-((dimethylamino)methylene)amino)picolinate (5.1 g, crude, 17.82 mmol) was dissolved in ethanol (50 mL). Sodium acetate (2.92 g, 35.65 mmol) and hydroxylamine hydrochloride (2.48 g, 35.65 mmol) were then added. The mixture was stirred at 50°C for 4 hours. The crude reaction solution was concentrated to give crude product methyl (E)-5-bromo-6-(N'-hydroxycarbamimidoyl)picolinate (10 g, yellow oil, crude), which was used directly in the next step without purification. MS m / z (ESI): 273.8 [M+H]+. Step 3: Methyl (E)-5-bromo-6-(N'-hydroxycarbamimidoyl)picolinate (10.0 g, crude) was dissolved in tetrahydrofuran (100 mL). Trifluoroacetic anhydride (17.30 g, 35.65 mmol) was then added. The mixture was stirred at 75°C for 3 hours. After cooling to room temperature, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution (30 mL), extracted with ethyl acetate (20 mLx3). The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and the solvent was concentrated. The resultant was purified by silica gel column chromatography (PE / EA = 50 / 50) to give methyl 8-bromo-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylate (3.55 g, white solid, 80.0% yield over three steps). MS m / z (ESI): 258.0 [M+H]+. Step 4: At 25°C under a nitrogen atmosphere, 8-bromo-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)imidazo[1,5-c]pyrimidin-5-amine (1.50 g, 4.13 mmol), potassium acetate (1.22 g, 12.39 mmol), and bis(pinacolato)diboron (2.10 g, 8.26 mmol) were dissolved in 1,4-dioxane (50 mL). Tetrakis(triphenylphosphine)palladium(0) (0.95 g, 0.83 mmol) was then added in one portion, and the mixture was stirred at 100°C for 18 hours. The crude reaction solution was concentrated to give a crude product. The crude product was purified by silica gel chromatography (eluent: dichloromethane:methanol = 1:0 to 10:1) to give N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,5-c]pyrimidin-5-amine (400.0 mg, yellow solid). Yield: 23.61%. MS m / z (ESI): 411.2 [M+H]+. Step 5: At 25°C under a nitrogen atmosphere, N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,5-c]pyrimidin-5-amine (370 mg, 0.90 mmol), methyl 8-bromo-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylate (461.9 mg, 1.80 mmol), and potassium carbonate (373.9 mg, 2.71 mmol) were dissolved in dimethoxyethane (20 mL) and water (2 mL). Tetrakis(triphenylphosphine)palladium(0) (104.2 mg, 0.09 mmol) was then added in one portion, and the mixture was stirred at 80°C for 2 hours. The crude reaction solution was concentrated to give a crude product. The crude product was purified by silica gel chromatography (eluent: dichloromethane:methanol = 1:0 to 10:1) to give methyl 8-(5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino)imidazo[1,5-c]pyrimidin-8-yl)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylate (16.0 mg, yellow solid). Yield: 38.61%. MS m / z (ESI): 460.2 [M+H]+. Step 6: At 25°C under a nitrogen atmosphere, methyl 8-(5-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino)imidazo[1,5-c]pyrimidin-8-yl)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylate (53 mg, 0.12 mmol) and lithium hydroxide (24.2 mg, 0.58 mmol) were dissolved in methanol (2 mL) and water (0.5 mL). The mixture was stirred at 25°C for 2 hours. The crude reaction solution was concentrated to give a crude product. The crude product was used directly in the next step. MS m / z (ESI): 446.2 [M+H]+. Preparation of Intermediate 5'-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-7'-oxo-spiro[indene-1,8'-pyrido[4,3-c]pyridazine]-5-carboxylic acid Step 1: Compound 5-bromoindane-1-carbonitrile (3.0 g, 13.51 mmol) was dissolved in methanol (100 mL). Under argon protection, molybdenum hexacarbonyl (5.35 g, 20.26 mmol), triethylamine (5.46 g, 54.03 mmol, 7.52 mL), palladium acetate (303.28 mg, 1.35 mmol), and 1,1'-binaphthyl-2,2'-bis(diphenylphosphine) (1.68 g, 2.70 mmol) were added sequentially. The tube was sealed and heated to 70°C, and the mixture was stirred for 2 hours. The reaction solution was filtered, concentrated to dryness under reduced pressure, and purified by silica gel column chromatography (EA:PE = 0-50%) to give methyl 1-cyanoindane-5-carboxylate (600 mg, 2.98 mmol, 22.07% yield) as a yellow solid. MS m / z (ESI): 202 [M+H]+. Step 2: Methyl 1-cyanoindane-5-carboxylate (1.0 g, 4.97 mmol) was dissolved in tetrahydrofuran (20 mL). Under argon protection, the temperature was lowered to 0°C, and sodium hydride (795.07 mg, 19.88 mmol, 60% purity) was added portionwise. After addition, the mixture was stirred at 0°C for 1 hour. 3-Chloropyridazine-4-carbonitrile (832.17 mg, 5.96 mmol) dissolved in tetrahydrofuran (5 mL) was added dropwise. After addition, the mixture was stirred at 0°C for 2 hours, then naturally warmed to room temperature and stirred overnight. The reaction solution was poured into ice water, extracted with EA (30 mL*2), dried over anhydrous sodium sulfate, concentrated to dryness under reduced pressure, and purified by silica gel column chromatography (EA:PE = 0-100%) to give methyl 1-cyano-1-(4-cyanopyridazin-3-yl)indane-5-carboxylate (300 mg, 985.86 pmol, 19.84% yield) as a yellow solid. MS m / z (ESI): 305 [M+H]+. Step 3: Methyl 1-cyano-1-(4-cyanopyridazin-3-yl)indane-5-carboxylate (300 mg, 985.86 pmol) was dissolved in concentrated hydrochloric acid (97.15 mg, 985.86 pmol, 15 mL, 37% purity). The mixture was heated to 80°C and stirred for 2 hours. The reaction solution was concentrated to dryness under reduced pressure to give 5',7'-dioxospiro[indene-1,8'-pyrido[4,3-c]pyridazine]-5-carboxylic acid (304.90 mg, 985.85 pmol, 100.00% yield) as a gray solid. MS m / z (ESI): 305 [M+H]+. Step 4: 5',7'-Dioxospiro[indene-1,8'-pyrido[4,3-c]pyridazine]-5-carboxylic acid (300 mg, 970.01 pmol) was dissolved in tetrahydrofuran (10 mL). 2-tert-Butyl-1,3-diisopropylisourea (971.56 mg, 4.85 mmol) was added, and the mixture was stirred at room temperature, and the mixture was stirred at room temperature for 16 hours. The reaction solution was concentrated to dryness under reduced pressure and purified by silica gel column chromatography (EA:PE = 0-100%) to give tert-butyl 5',7'-dioxospiro[indene-1,8'-pyrido[4,3-c]pyridazine]-5-carboxylate (320 mg, 875.80 pmol, 90.29% yield) as a yellow solid. MS m / z (ESI): 366 [M+H]+. Step 5: tert-Butyl 5',7'-dioxospiro[indene-1,8'-pyrido[4,3-c]pyridazine]-5-carboxylate (226.03 mg, 618.62 pmol) was dissolved in acetonitrile (10 mL). Under argon protection, phosphorus oxychloride (474.27 mg, 3.09 mmol) and diisopropylethylamine (799.52 mg, 6.19 mmol, 1.08 mL) were added. The mixture was heated to 80°C and stirred for 25 minutes, then cooled to room temperature. (5-Fluoro-2,3-dihydrobenzofuran-4-yl)methanamine (517.10 mg, 3.09 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated to dryness under reduced pressure and purified by silica gel column chromatography (MeOH:DCM = 0-10%) to give tert-butyl 5'-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-7'-oxospiro[indene-1,8'-pyrido[4,3-c]pyridazine]-5-carboxylate (60 mg, 116.61 pmol, 18.85% yield) as a yellow solid. MS m / z (ESI): 515 [M+H]+. Step 6: tert-Butyl 5'-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-7'-oxospiro[indene-1,8'-pyrido[4,3-c]pyridazine]-5-carboxylate (50 mg, 97.17 pmol) was dissolved in dichloromethane (10 mL). A solution of hydrogen chloride in ethyl acetate (4.0 M, 10.00 mL) was added, and the mixture was stirred at room temperature, and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated to dryness under reduced pressure to give 5'-[(5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamino]-7'-oxo-spiro[indene-1,8'-pyrido[4,3-c]pyridazi ne]-5-carboxylic acid (44.55 mg, 97.18 pmol, 100.00% yield) as a yellow solid. MS m / z (ESI): 459 [M+H]+. Preparation of Intermediate 2-(2,6-dioxopiperidin-3-yl)-5-(3,9-diazaspiro[5.5]undecan-3-yl)isoindoline-1,3-dione Step 1: 2-(2,6-Dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione (500 mg, 1.81 mmol) and tert-butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (506.49 mg, 1.99 mmol) were dissolved in DMSO (5 mL). DIPEA (467.90 mg, 3.62 mmol, 630.59 pL) was added. The mixed solution was stirred at 90°C under nitrogen protection for 15 hours, and the starting material was completely reacted. H2O (50 mL) was added to the reaction solution, the mixture was extracted three times with ethyl acetate (25 mL*3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to dryness under reduced pressure to give a crude product. The crude product was purified by combiflash (EA:PE =   0-60%) to give tert-butyl 9-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate (765 mg, yield: 82.77%) as a yellow oil. MS m / z (ESI): 510.9 [M+H]+. Step       2:       tert-Butyl       9-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-3,9- diazaspiro[5.5]undecane-3-carboxylate (715 mg, 1.40 mmol) was dissolved in dioxane (10 mL). A solution of HCl in dioxane (4 M, 10 mL) was added at room temperature (25°C). The mixed solution was stirred at room temperature (25°C) for 5 hours, and the starting material was completely reacted. The reaction solution was concentrated to dryness under reduced pressure to give crude product 2-(2,6-dioxopiperidin-3-yl)-5-(3,9-diazaspiro[5.5]undecan-3-yl)isoindoline-1,3-dione (570 mg, crude), which was used directly in the next step without further purification. MS m / z (ESI): 411.2 [M+H]+. Preparation of Intermediate 1-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)piperidine-4-carbaldehyde Step 1: 3-(5-Bromo-3-methyl-2-oxo-benzimidazol-1-yl)piperidine-2,6-dione (5.0 g, 14.79 mmol) and 4-(dimethoxymethyl)piperidine (4.71 g, 29.57 mmol) were dissolved in toluene (150 mL). Under argon        protection,        methanesulfonato(2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'- biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (2.48 g, 2.96 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (1.38 g, 2.96 mmol), and lithium bis(trimethylsilyl)amide (1.0 M, 73.93 mL) were added sequentially. The mixture was heated to 80°C and stirred for 2 hours. The reaction solution was poured into saturated ammonium chloride solution and extracted with ethyl acetate (30 mL*2). The organic phase was dried over anhydrous sodium sulfate, concentrated to dryness under reduced pressure, and purified by silica gel column chromatography (EA:PE = 0-100%) to give 3-[5-[4-(dimethoxymethyl)piperidin-1-yl]-3-methyl-2-oxo-benzimidazol-1-yl]piperidine-2,6-dione as a yellow solid. MS m / z (ESI): 417 [M+H]+. Step 2: 3-[5-[4-(Dimethoxymethyl)piperidin-1-yl]-3-methyl-2-oxo-benzimidazol-1-yl]piperidine-2,6-dione (5.3 g, 12.73 mmol) was dissolved in formic acid (122.00 g, 2.65 mol, 100 mL), and the mixture was stirred at 50°C for 1 hour. After the reaction was complete, the solvent was dried by rotary evaporation under reduced pressure to give 1-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)piperidine-4-carbaldehyde (4.71 g, 12.72 mmol, 100.00% yield) as a red solid. MS m / z (ESI): 371 [M+H]+. Preparation of Intermediate   1-(3-(2,6-dioxopiperidin-3-yl)-5-fluoro-1-methyl-1H-indazol-6- yl)piperidine-4-carbaldehyde Step 1: Compound 6-bromo-5-fluoro-1-methyl-1H-indazole (1140 mg, 5 mmol) was added to 5 ml of DMSO. N-Iodosuccinimide (1125 mg, 5 mmol) was then added, and the mixture was heated to 120°C and stirred for 3 hours. After the reaction was complete, the mixture was poured into water, extracted three times with 30 ml of ethyl acetate. The organic phases were combined, washed once with 50 ml of saturated sodium chloride, and the organic phase was concentrated to give compound 6-bromo-5-fluoro-3-iodo-1-methyl-1H-indazole (1239 mg, 3.5 mmol). Yield: 70%. MS m / z (ESI): 354.9 [M+H]+. Step 2: Compound 6-bromo-5-fluoro-3-iodo-1-methyl-1H-indazole (1239 mg, 3.5 mmol), 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1460 mg, 3.5 mmol), 120 mg of Pd(dppf)Cl2, and 3.41 g of cesium carbonate were sequentially added to 10 ml of 1,4-dioxane. Then, 2 ml of water was added, and the mixture was purged with nitrogen three times. The mixture was then heated to 110°C and stirred for 15 hours. After the reaction was complete, the mixture was poured into water, extracted three times with 30 ml of ethyl acetate. The organic phases were combined, washed once with 50 ml of saturated sodium chloride. An appropriate amount of silica gel was added to the obtained organic phase for sample loading, and the resultant was purified by column chromatography      using      PE / EA      (0-50%)      to      give      compound 3-(2,6-bis(benzyloxy)pyridin-3-yl)-6-bromo-5-fluoro-1-methyl-1H-indazole (1036 mg, 2 mmol). Yield: 57%. MS m / z (ESI): 518 [M+H]+. Step 3: Compound 3-(2,6-bis(benzyloxy)pyridin-3-yl)-6-bromo-5-fluoro-1-methyl-1H-indazole (1036 mg, 2 mmol) was added to 5 ml of methanol. Then, 200 mg of 10 wt% Pd / C was added, and the mixture was purged with hydrogen three times and then stirred at room temperature for 3 hours. After the reaction was complete, the mixture was filtered, and the filtrate was concentrated to give compound 3-(6-bromo-5-fluoro-1-methyl-1H-indazol-3-yl)piperidine-2,6-dione (680 mg, 2 mmol). Yield: 100%. MS m / z (ESI): 340 [M+H]+. Step 4: Compound 3-(6-bromo-5-fluoro-1-methyl-1H-indazol-3-yl)piperidine-2,6-dione (680 mg, 2 mmol), 4-(dimethoxymethyl)piperidine (477 mg, 3 mmol), 340 mg of Ruphos-Pd-G3, and cesium carbonate (1952 mg, 6 mmol) were sequentially added to 10 ml of 1,4-dioxane. The mixture was purged with nitrogen three times, the mixture was heated to 120°C and stirred for 15 hours. After the reaction was complete, the mixture was poured into water, then extracted three times with 30 ml of ethyl acetate. The organic phases were combined, washed once with 50 ml of saturated brine. An appropriate amount of silica gel was added to the organic phase for sample loading, and the resultant was purified by column chromatography using PE / EA (0-100%) to give 3-(6-(4-(dimethoxymethyl)piperidin-1-yl)-5-fluoro-1-methyl-1H-indazol-3-yl)piperidine-2,6-dione (84 mg, 0.2 mmol). Yield: 10%. MS m / z (ESI): 419 [M+H]+. Step 5: Compound 3-(6-(4-(dimethoxymethyl)piperidin-1-yl)-5-fluoro-1-methyl-1H-indazol-3-yl)piperidine-2,6-dione (84 mg, 0.2 mmol) was added to 5 ml of dichloromethane. Then, 2 ml of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was dried under oil pump vacuum to give 1-(3-(2,6-dioxopiperidin-3-yl)-5-fluoro-1-methyl-1H-indazol-6-yl)piperidine-4-carbaldehyde (74.5 mg, 0.2 mmol). Yield: 100%. MS m / z (ESI): 373 [M+H]+. Preparation of Intermediate 1-(3-(2,6-dioxopiperidin-3-yl)-1-methyl-1H-indazol-6-yl)piperidine-4-carbaldehyde Step 1: 6-Bromo-3-iodo-1-methylindazole (3000 mg, 8.90 mmol) was dissolved in 24 mL of 1,4-dioxane and water (8 mL). Then, 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl...

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof:POI—(L)n0—ULM(I),wherein, POI is a ligand that binds to an EED protein;L is a linker connecting POI and ULM;ULM is a group that binds to an E3 ligase; andn0 is 0 or 1.

2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein POI is a structure of formula (A-1) or an isomer thereof:(A-1)wherein,ring A1 is a 5- to 20-membered heterocycloalkyl ring (preferably a 5- to 6-membered heterocycloalkyl ring, preferably a 15- to 20-membered heterocycloalkyl ring, more preferably a 15- to 18-membered heterocycloalkyl ring, further preferably an 18-membered heterocycloalkyl ring) or a 5-to 10-membered heteroaryl ring;ring A2 is absent, or is a 3- to 15-membered heterocycloalkyl ring, a C3-10 cycloalkyl ring, a 5- to 15-membered heteroaryl ring (preferably a 5- to 12-membered heteroaryl ring, more preferably a 5- to 10-membered heteroaryl ring, further preferably a 5- to 6-membered heteroaryl ring) or a C6-10 aryl ring (preferably a benzene ring or a naphthalene ring);(R1)n1 represents substitution of hydrogen on 2,3-dihydrobenzofuran ring by n1 R1, n1 is 0, 1 or 2, each R1 is identical or different, and each R1 is independently selected from the group consisting of hydrogen, deuterium, halogen (preferably fluorine, chlorine, or bromine), oxo, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy), -COC1-8 alkyl (preferably -COC1-6 alkyl, more preferably -COC1-3 alkyl), -OCOC1-8 alkyl (preferably -OCOC1-6 alkyl, more preferably -OCOC1-3 alkyl), -COOC1-8 alkyl (preferably -COOC1-6 alkyl, more preferably -COOC1-3 alkyl), -CONH2, -CONHC1-8 alkyl (preferably -CONHC1-6 alkyl, more preferably -CONHC1-3 alkyl), -CON(C1-8 alkyl)2 (preferably -CON(C1-6 alkyl)2, more preferably -CON(C1-3 alkyl)2), -SOC1-8 alkyl (preferably -SOC1-6 alkyl, more preferably -SOC1-3 alkyl), -SO2C1-8 alkyl (preferably -SO2C1-6 alkyl, more preferably -SO2C1-3 alkyl), -OSO2C1-8 alkyl (preferably -OSO2C1-6 alkyl, more preferably -OSO2C1-3 alkyl), -SO2NH2, -SO2NHC1-8 alkyl (preferably -SO2NHC1-6 alkyl, more preferably-SO2NHC1-3 alkyl), -SO2N(C1-8 alkyl)2 (preferably -SO2N(C1-6 alkyl)2, more preferably -SO2N(C1-3 alkyl)2), C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl); and / or two R1 and carbon atom linked to the two R1 together form a C3-15 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring) or a 3- to 15-membered heterocycloalkyl ring (preferably a 3- to 10-membered heterocycloalkyl ring, more preferably a 3- to 8-membered heterocycloalkyl ring, further preferably a 3- to 6-membered heterocycloalkyl ring); the C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, -COC1-8 alkyl, -COOC1-8 alkyl, -OCOC1-8 alkyl, -CONH2, -CONHC1-8 alkyl, -CON(C1-8 alkyl)2, -SOC1-8 alkyl, -SO2C1-8 alkyl, -OSO2C1-8 alkyl, -SO2NH2, -SO2NHC1-8 alkyl, -SO2N(C1-8 alkyl)2, C3-8 cycloalkyl, 3- to 12-membered heterocycloalkyl, 5- to 10-membered heteroaryl, C6-14 aryl, C3-15 cycloalkyl ring and 3- to 15-membered heterocycloalkyl ring are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of halogen, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl) and 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl);(R2)n2 represents substitution of hydrogen on ring A1 by n2 R2, n2 is 0, 1 or 2, each R2 is identical or different, and each R2 is independently selected from the group consisting of X1, hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy), -NHC1-8 alkyl (preferably -NHC1-6 alkyl, more preferably -NHC1-3 alkyl), -N(C1-8 alkyl)2 (preferably -N(C1-6 alkyl)2, more preferably -N(C1-3 alkyl)2), -COC1-8 alkyl (preferably -COC1-6 alkyl, more preferably -COC1-3 alkyl), -OCOC1-8 alkyl (preferably -OCOC1-6 alkyl, more preferably -OCOC1-3 alkyl), -COOC1-8 alkyl (preferably -COOC1-6 alkyl, more preferably -COOC1-3 alkyl), -CONH2, -CONHC1-8 alkyl (preferably -CONHC1-6 alkyl, more preferably -CONHC1-3 alkyl), -CON(C1-8 alkyl)2 (preferably -CON(C1-6 alkyl)2, more preferably -CON(C1-3 alkyl)2), -PO(C1-8 alkyl)2 (preferably -PO(C1-6 alkyl)2, more preferably -PO(C1-3 alkyl)2), -SOC1-8 alkyl (preferably -SOC1-6 alkyl, more preferably -SOC1-3 alkyl), -SO2C1-8 alkyl (preferably -SO2C1-6 alkyl, more preferably -SO2C1-3 alkyl), -OSO2C1-8 alkyl (preferably -OSO2C1-6 alkyl, more preferably -OSO2C1-3 alkyl), -SC1-6 alkyl, -SO2NH2, -SO2NHC1-8 alkyl (preferably -SO2NHC1-6 alkyl, more preferably -SO2NHC1-3 alkyl), -SO2N(C1-8 alkyl)2 (preferably -SO2N(C1-6 alkyl)2, more preferably -SO2N(C1-3 alkyl)2), C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl),5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl); the C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, -NHC1-8 alkyl, -N(C1-8 alkyl)2, -COC1-8 alkyl, -OCOC1-8 alkyl, -COOC1-8 alkyl, -CONH2, -CONHC1-8 alkyl, -CON(C1-8 alkyl)2, -PO(C1-8 alkyl)2, -SOC1-8 alkyl, -SO2C1-8 alkyl, -OSO2C1-8 alkyl, -SO2NH2, -SO2NHC1-8 alkyl,-SO2N(C1-8 alkyl)2, C3-8 cycloalkyl, 3- to 12-membered heterocycloalkyl, 5- to 10-membered heteroaryl and C6-14 aryl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of halogen, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -PO(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl);or R1, R2 and carbon atom linked to R1 and R2 together form a 6- to 15-membered heterocycloalkyl ring; the 6- to 15-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of halogen, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -PO(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 12-membered heterocycloalkyl (preferably 4- to 8-membered heterocycloalkyl, more preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl (preferably C6-12 aryl);(R3)n3 represents substitution of hydrogen on ring A2 by n3 R3, n3 is 0, 1, 2 or 3, each R3 is identical or different, and each R3 is independently selected from the group consisting of X1, hydrogen, deuterium, cyano, carboxyl, nitro, formyl, sulfo, halogen, oxo, C1-10 alkyl (preferably C1-8 alkyl, more preferably C1-6 alkyl, further preferably C1-3 alkyl), C1-10 haloalkyl (preferably C1-8 haloalkyl, more preferably C1-6 haloalkyl, further preferably C1-3 haloalkyl), C1-10 alkoxy (preferably C1-8 alkoxy, more preferably C1-6 alkoxy, further preferably C1-3 alkoxy), C1-10 haloalkoxy (preferably C1-8 haloalkoxy, more preferably C1-6 haloalkoxy, further preferably C1-3 haloalkoxy), -COC1-10 alkyl (preferably -COC1-8 alkyl, more preferably -COC1-6 alkyl, further preferably -COC1-3 alkyl), -OCOC1-10 alkyl (preferably -OCOC1-8 alkyl, more preferably -OCOC1-6 alkyl, further preferably -OCOC1-3 alkyl), -COOC1-10 alkyl (preferably -COOC1-8 alkyl, more preferably -COOC1-6 alkyl, further preferably -COOC1-3 alkyl), -CONH2, -CONHC1-10 alkyl (preferably -CONHC1-8 alkyl, more preferably -CONHC1-6 alkyl, further preferably -CONHC1-3 alkyl), -CON(C1-10 alkyl)2 (preferably -CON(C1-8 alkyl)2, more preferably -CON(C1-6 alkyl)2, further preferably -CON(C1-3 alkyl)2), -SOC1-10 alkyl (preferably -SOC1-8 alkyl, more preferably -SOC1-6 alkyl, further preferably -SOC1-3 alkyl), -SO2C1-10 alkyl (preferably -SO2C1-8 alkyl, more preferably -SO2C1-6 alkyl, further preferably -SO2C1-3 alkyl),-OSO2C1-10 alkyl (preferably -OSO2C1-8 alkyl, more preferably -OSO2C1-6 alkyl, further preferably -OSO2C1-3 alkyl), -SO2NH2, -SO2NHC1-10 alkyl (preferably -SO2NHC1-8 alkyl, more preferably-SO2NHC1-6 alkyl, further preferably -SO2NHC1-3 alkyl), -SO2N(C1-10 alkyl)2 (preferably -SO2N(C1-8 alkyl)2, more preferably -SO2N(C1-6 alkyl)2, further preferably -SO2N(C1-3 alkyl)2), C3-8 cycloalkyl (preferably C3-6 cycloalkyl), 3- to 15-membered heterocycloalkyl (preferably 4- to 12-membered heterocycloalkyl, more preferably 4- to 8-membered heterocycloalkyl, further preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl) and C6-14 aryl; the C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, C1-10 haloalkoxy, -COC1-10 alkyl, -OCOC1-10 alkyl, -COOC1-10 alkyl, -CONH2, -CONHC1-10 alkyl, -CON(C1-10 alkyl)2, -SOC1-10 alkyl, -SO2C1-10 alkyl, -OSO2C1-10 alkyl, -SO2NH2, -SO2NHC1-10 alkyl, -SO2N(C1-10 alkyl)2, C3-8 cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 10-membered heteroaryl and C6-14 aryl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, C3-6 cycloalkyl, 3- to 15-membered heterocycloalkyl (preferably 4- to 12-membered heterocycloalkyl, more preferably 4- to 8-membered heterocycloalkyl, further preferably 4- to 6-membered heterocycloalkyl), 5- to 10-membered heteroaryl (preferably 5- to 6-membered heteroaryl), phenyl and naphthyl;X1 in R2 and R3 is a point of attachment of POI to L or ULM, and at least one of R2 and R3 is X1.

3. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein ring A1 is an 8- to 10-membered heteroaryl ring, a 5- to 6-membered heterocycloalkyl ring or an 18-membered heterocycloalkyl ring;preferably, ring A1 is a 9-membered heteroaryl ring or a 10-membered heteroaryl ring;preferably, ring A1 is a 9-membered nitrogen-containing heteroaryl ring or a 10-membered nitrogen-containing heteroaryl ring;preferably, ring A1 is selected from the group consisting of an indolizine ring, a pyrazolopyridine ring, an imidazopyridine ring, a triazolopyridine ring, a tetrazolopyridine ring, a pyrrolopyridazine ring, a pyrazolopyridazine ring, an imidazopyridazine ring, a triazolopyridazine ring, a tetrazolopyridazine ring, a pyrrolopyrimidine ring, a pyrazolopyrimidine ring, an imidazopyrimidine ring, a triazolopyrimidine ring, a tetrazolopyrimidine ring, a pyrrolopyrazine ring, a pyrazolopyrazine ring, an imidazopyrazine ring, a triazolopyrazine ring, a pyridopyridine ring, a pyridopyrazine ring, a pyridopyridazine ring, a pyridotriazine ring, a pyridopyrimidine ring and a tetrazolopyrazine ring;preferably, ring A1 is selected from the group consisting of [1,2,4]triazolo[4,3-c]pyrimidine, imidazo[1,5-c]pyrimidine,      imidazo[1,2-c]pyrimidine,      [1,2,4]triazolo[4,3-a]pyridine     andpyrido[3,4-d]pyridazine;preferably, ring A1 is selected from the group consisting of pyrimidin-4(3H)-one, 1,6-dihydropyrimidine, pyridin-2(1H)-one, 1,2-dihydropyridine and 3,8-diazabicyclo[3.2.1]octane;preferably, ring A1 is a partially unsaturated 18-membered heterocycloalkyl ring;preferably, ring A1 is selected from the group consisting of2,3-dihydro-7'H-spiro[indene-1,8'-pyrido[3,4-d]pyridazin]-7'-one                                and2,3-dihydro-7'H-spiro[indene-1,8'-pyrido[4,3-c]pyridazin]-7'-one.

4. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, whereinfollowing structures or isomers thereof:is selected from the group consisting of the1015isomers thereof:isomers thereof:isomers thereof:andpreferably,preferably,is selected from thepreferably,is selected from theis selected from the group consistingof the followingstructures orandgroup consisting of the following structures orandgroup consisting of the following structures or5. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein POI is a structure of formula (A-2-1) or an isomer thereof:(A-2-1)wherein, W1, W2, W3, W4, W5 and W6 are each independently CH or N, ring A2, R1, n1, R2, n2,R3 and n3 are as defined in claim 2, and at least one of R2 and R3 is X1;preferably, POI is a structure of formula (A-2-2) or an isomer thereof:(A-2-2)wherein, W1, W2, W3, W4 and W5 are each independently CH or N; ring A2, R1, n1, R2, n2, R3 and n3 are as defined in claim 2, and at least one of R2 and R3 is X1.

6. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein POI is selected from the group consisting of the following structures or isomers thereof:wherein, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in claim 2, and at least one of R2 and R3 is X1.

7. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein ring A2 is absent or is selected from the group consisting of a 4- to 8-membered heterocycloalkyl ring, a C4-8 cycloalkyl ring, a 5- to 10-membered heteroaryl ring, a 10- to 15-membered heterocycloalkyl ring and a benzene ring;preferably, ring A2 is absent or is selected from the group consisting of a 4- to 8-membered heterocycloalkyl ring, a saturated C4-8 cycloalkyl ring, a 5- to 10-membered heteroaryl ring, a partially unsaturated 10- to 15-membered heterocycloalkyl ring and a benzene ring;preferably, ring A2 is absent, or is selected from the group consisting of a cyclobutane ring, acyclopentane ring, a cyclohexane ring, an azetidine ring, a tetrahydropyrrole ring, a pyrazolidine ring, an imidazolidine ring, a piperidine ring, a hexahydropyridazine ring, a hexahydropyrimidine ring, a piperazine ring, a benzene ring, a pyrazole ring, an oxazole ring, an imidazole ring, a triazole ring, a tetrazole ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, an indolizine ring, pyrazolopyridine,    imidazopyridine,    triazolopyridine,   tetrazolopyridine,   pyrrolopyridazine,pyrazolopyridazine, imidazopyridazine, triazolopyridazine, tetrazolopyridazine, pyrrolopyrimidine, pyrazolopyrimidine, imidazopyrimidine, triazolopyrimidine, tetrazolopyrimidine, pyrrolopyrazine, pyrazolopyrazine, imidazopyrazine, triazolopyrazine, tetrazolopyrazine, pyridopyridine, pyridopyrazine, pyridopyridazine, pyridotriazine, pyridopyrimidine, 3,8-diazabicyclo[3.2.1]octane and 2,3-dihydrospiro[indene-1,4'-piperidine];preferably, ring A2 is absent or is selected from the group consisting of a saturated 6-membered heterocycloalkyl ring, a partially unsaturated 12-membered heterocycloalkyl ring, a cyclohexane ring, a 5- to 6-membered heteroaryl ring, a 9-membered heteroaryl ring and a benzene ring;preferably, ring A2 is absent or is selected from the group consisting of a cyclohexane ring, a piperidine ring, a piperazine ring, a benzene ring, a pyridine ring, a pyrazole ring, a triazolopyridine ring and 2,3-dihydrospiro[indene-1,4'-piperidine];preferably, ring A2 is selected from the group consisting of a benzene ring, a pyridine ring and a pyrazole ring.

8. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, whereinis selected from the group consisting of thefollowing structures or isomers thereof:is selected from the group consisting of the following structures:andpreferably,preferably,is selected from the group consisting of the following structures orisomers thereof:preferably,is selected from the group consisting of the following structures or isomersthereof:and9. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R1 is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, propoxy, isopropoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, pyrrolyl, pyrazolyl, pyridinyl, phenyl, pyrimidinyl, -CH2-cyclopropyl, -CH2-tetrahydropyrrolyl, -CH2-pyrrolyl, -CH2-phenyl, -CH2-pyridinyl, -CH2-cyclohexenyl, -CH2-azetidine, -CH2-piperidine, -CH2-piperazine, tetrahydro-2H-pyran and -CH2-(tetrahydro-2H-pyran); or two R1 and carbon atom linked to the two R1 together form a cyclopropyl ring, a cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring, a cyclobutene ring, a cyclopentene ring, a cyclohexene ring, an azetidine ring, a tetrahydropyrrole ring, a piperidine ring or a piperazine ring;preferably, R1 is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, iodine, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH2F, -CHF2, -CF3, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2,  -OCH2F, -OCHF2,  -OCF3,  -CH2CH2F, -CH2CHF2,  -CH2CF3,-OCH2CH2F, -OCH2CHF2 and -OCH2CF3;preferably, two R1 and carbon atom linked to the two R1 together form a cyclopropyl ring;preferably, R1 is fluorine.

10. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt11. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R2 is selected from the group consisting of X1, hydrogen,deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -PO(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SC1-6 alkyl, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl and C1-6 haloalkoxy;preferably, R2 is selected from the group consisting of X1, hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -COC1-3 alkyl, -COOC1-3 alkyl, -OCOC1-3 alkyl, -PO(C1-3 alkyl)2, -SOC1-3 alkyl, -SO2C1-3 alkyl, -OSO2C1-3 alkyl, -SC1-3 alkyl, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl and C1-3 haloalkoxy;preferably, R2 is selected from the group consisting of X1, hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, amino, oxo, -NHCH3, -N(CH3)2, -CONH2, -CONHCH3, -CON(CH3)2, -COCH3, -COC(CH3)3, -COOCH3, -COOCH2CH3, -COOC(CH3)3, -OCOCH3, -OCOCH2CH3, -OCOC(CH3)3, -PO(CH3)2, -PO(CH2CH3)2, -SOCH3, -SOCH2CH3, -SOC(CH3)3, -SO2CH3, -SO2CH2CH3, -SO2C(CH3)3, -OSO2CH3, -OSO2CH2CH3, -OSO2C(CH3)3, -SCH3, -SCH2CH3, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, monofluoropropyl, difluoropropyl, trifluoropropyl, monofluoroisopropyl, difluoroisopropyl, trifluoroisopropyl, monofluoro-tert-butyl, difluoro-tert-butyl, trifluoro-tert-butyl, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, monofluoropropoxy, difluoropropoxy, trifluoropropoxy, monofluoroisopropoxy, difluoroisopropoxy, trifluoroisopropoxy, monofluoro-tert-butoxy, difluoro-tert-butoxy and trifluoro-tert-butoxy;preferably, R2 is selected from the group consisting of cyano, fluorine, chlorine, bromine, iodine, -CH3, -CF3, -SO2CH3 and hydrogen;preferably, R2 is selected from the group consisting of cyano, fluorine, chlorine, bromine, iodine, -SO2CH3 and hydrogen;preferably, R2 is selected from the group consisting of X1, hydrogen, halogen, cyano, -SO2C1-6 alkyl and -OSO2C1-6 alkyl;preferably, R2 is selected from the group consisting of X1, hydrogen, halogen, cyano, -SO2C1-3 alkyl and -OSO2C1-3 alkyl;preferably, R2 is selected from the group consisting of X1, hydrogen, fluorine, chlorine, bromine, iodine, cyano, -SO2CH3 and -OSO2CH3.

12. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt (R2)n2thereof, or a stereoisomer thereof, wherein X' N hnX^\ following structures or isomers thereof:       n A1 / 1 -X   is selected from the group consisting of the N>    ■A     / n      A Xi x X x ~x  XN \ X xx H,ix XX ,,   ,   ,10preferably,isomers thereof:and; wherein X1 is the point of attachment to L or ULM;is selected from the group consisting of the following structures orpreferably,isomers thereof:preferably,and; wherein X1 is the point of attachment to L or ULM;is selected from the group consisting of the following structures orandis selected from the group consisting of the following structures orisomers thereof:andpreferably,is selected from the group consisting of the following structures orisomers thereof:and13. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R1, R2 and carbon atom linked to R1 and R2 together form a 6- to 15-membered heterocycloalkyl ring, the 6- to 15-membered heterocycloalkyl ring is selected from the group consisting of 5,8-dihydro-4H-1,4-oxazocine, 4,5,8,9-tetrahydro-1,4-oxazepine, 5,8,9,10-tetrahydro-4H-1,4-oxazonine, and 1-oxa-4-azacycloundeca-2,6-diene; the 6- to 15-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, methyl, ethyl, isopropyl, tert-butyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, isopropoxy, tert-butoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, -COCH3, -COCH2CH3, -COCH(CH3)2, -COC(CH3)3, -OCOCH3, -OCOCH2CH3,-OCOCH(CH3)2, -OCOC(CH3)3,  -CONH2, -CONHCH3, -CONHCH2CH3, -CONHCH(CH3)2,-CONHC(CH3)3, -CON(CH3)2, -CON(CH2CH3)2, -SOCH3, -SO2CH3, -SO2CH2CH3, -SO2CH(CH3)2, -SO2C(CH3)3, -OSO2CH3, -OSO2CH2CH3, -OSO2CH(CH3)2, -OSO2C(CH3)3, -SO2NH2, -SO2NHCH3, -SO2NHCH2CH3, -SO2NHCH(CH3)2, -SO2NHC(CH3)3, -SO2N(CH3)2, -SO2N(CH2CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, azetidinyl, tetrahydropyrrolyl, piperidinyl, piperazinyl, pyrrolyl, pyrazolyl, pyridinyl, phenyl and pyrimidinyl;preferably, R1, R2 and carbon atom  linked to R1 and R2 together form(2Z,6Z)-4,5,8,9-tetrahydro-1,4-oxazepine,                   (2E,6Z)-4,5,8,9-tetrahydro-1,4-oxazepine,(2E,6E)-4,5,8,9-tetrahydro-1,4-oxazepine,                   (2Z,6E)-4,5,8,9-tetrahydro-1,4-oxazepine,(2Z,6Z)-5,8-dihydro-4H-1,4-oxazocine,                      (2E,6Z)-5,8-dihydro-4H-1,4-oxazocine,(2Z,6E)-5,8-dihydro-4H-1,4-oxazocine,                      (2E,6E)-5,8-dihydro-4H-1,4-oxazocine,(2Z,6Z)-5,8,9,10-tetrahydro-4H-1,4-oxazonine,        (2E,6Z)-5,8,9,10-tetrahydro-4H-1,4-oxazonine,(2Z,6E)-5,8,9,10-tetrahydro-4H-1,4-oxazonine,        (2E,6E)-5,8,9,10-tetrahydro-4H-1,4-oxazonine,(2Z,6Z)-1-oxa-4-azacycloundeca-2,6-diene,              (2E,6Z)-1-oxa-4-azacycloundeca-2,6-diene,(2Z,6E)-1-oxa-4-azacycloundeca-2,6-diene, or (2E,6E)-1-oxa-4-azacycloundeca-2,6-diene;preferably, R1, R2 and carbon atom linked to R1 and R2 together form (2Z,6Z)-4,5,8,9-tetrahydro-1,4-oxazepine,                    (2Z,6Z)-5,8-dihydro-4H-1,4-oxazocine,(2Z,6Z)-5,8,9,10-tetrahydro-4H-1,4-oxazonine, or (2Z,6Z)-1-oxa-4-azacycloundeca-2,6-diene.

14. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt O' / X (R?)n25   thereof, or a stereoisomer thereof, wherein                 H H 1 Hi- <R1>n1                 HN N                 / —V   A n2(R2) rAl||         \ / °       (R2)n2-■PaA      / " consisting of             °              , n2(R2)\.          Xj--(Rl)n1 XbX bl^O N-^       / V \ H         ' o--^ /          , wherein ------ represents ---- bond); n1 is 0 or 1, and n2 is 0 or 1; cXh      (R2>n2 (aX—\ (Rl)n1 \ J nX J preferably,                   h             is   selected (R2)n2 N__, z(R2)n2                                                  HN < n n Xa(Ri)"1                kJ i Y    \ p          V X Y i . A 1    \~J         X 0 10    V      0                  ,       <             (Rl)n1    , N % W ^-(R2)n2 r >-<Ri>ni £ / ~~N     1 JI iYn-^7;)5 \ H            ' o'"'''' /            ; wherein n1 is 0 or 1, and n2 is 0 or 1 is selected from the group (R2)n2 H \ N fj—(R')"1     V-x^N^As>'(R1)n1 I       iGY £ 0 o                     / , ,       o—7            and — (single bond) or ------ (double from   the   group   consisting   of N.I   H         / / V N  N ^As>r(Rl )m / o— /             andO'^l       (R2)n2 (Ri)ni \ J nA. y preferably,                   h           is   selected F n—.    H z                       '’S f~t "3 a XA "yA kz vb-j YY jO° Wy / J AX °          X                  o—' ,                                                          , n1 is 0 or 1, and n2 is 0 or 1; cXb      (R2)n2 ( aii—\ 1 c                       1       (Ri)ni             n x. y        ■      -.1..,. < 15         preferably,          x       h             is   selected from   the   group   consisting   of ^-N X'3     *~~XyX N,— -'^z             \ h   _—‘— / and                   ; wherein from   the   group   consisting   ofandwherein n1 is 0 or 1, and n2 is 0 or 1.

15. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R3 is selected from the group consisting of X1, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl; the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl,-CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl,-SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, halogen, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, -COC1-3 alkyl, -COOC1-3 alkyl, -CONH2, -CONHC1-3 alkyl, -CON(C1-3 alkyl)2, -SOC1-3 alkyl, -SO2C1-3 alkyl, -OSO2C1-3 alkyl, -SO2NH2, -SO2NHC1-3 alkyl, -SO2N(C1-3 alkyl)2, C3-6 cycloalkyl, 4- to 6-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl;preferably, R3 is selected from the group consisting of X1, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-memberedheteroaryl and phenyl; the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of cyano, hydroxyl, carboxyl, nitro, formyl, sulfo, halogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy, -COCH3, -OCOCH3, -COOCH3, -CONH2, -CONHCH3, -CON(CH3)2, -SOCH3, -SO2CH3, -SO2NH2, -SO2NHCH3,-SO2N(CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, azetidinyl, tetrahydropyrrolyl, piperidinyl, piperazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyrimidinyl, pyridazinyl and phenyl;preferably, R3 is selected from the group consisting of X1, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C3-8 cycloalkyl, -COC1-6 alkyl, -OCOC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -OSO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl, -SO2N(C1-6 alkyl)2, 4- to 8-membered heterocycloalkyl, 5- to 6-memberedheteroaryl and phenyl;preferably, R3 is selected from the group consisting of X1, fluorine, chlorine, bromine, iodine, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy, trifluoroethoxy, -COCH3, -COCH2CH3, -COC(CH3)3, -OCOCH3, -OCOCH2CH3, -OCOC(CH3)3,-COOCH3, -COOCH2CH3, -COOC(CH3)3, -CONH2, -CONHCH3, -CON(CH3)2, -SOCH3, -SO2CH3, -SO2C(CH3)3, -OSO2CH3, -OSO2C(CH3)3, -SO2NH2, -SO2NHCH3, -SO2N(CH3)2, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, azetidinyl, piperazinyl, piperidinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl and phenyl;preferably, R3 is selected from the group consisting of X1, C1-6 alkyl, C3-8 cycloalkyl, C1-6haloalkyl and -COC1-6 alkyl;preferably, R3 is selected from the group consisting of X1, C1-3 alkyl, C3-6 cycloalkyl, C1-3haloalkyl and -COC1-3 alkyl;preferably, R3 is selected from the group consisting of X1, methyl, cyclopropyl, trifluoromethyl and -COCH3;preferably, R3 is selected from the group consisting of X1, fluorine and methyl.

16. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable salt(R3)n31—(a thereof, or a stereoisomer thereof, wherein । following structures or isomers thereof: i / =\ x mAAaI p / / xi     ।  \    /             \     / —> N             *   \___ / ,                                                , aOh ,   ,, m          \           h         F3C L /         N-N      >n      An rv, v4Ay vAA va'a Xi \ -Z Xi \              X ,   ,, N^n        x H A N X.|        N'N'Xl        n Xt l         x 2) >     is selected from the group consisting of the N    « / =\        f=\         _ / ।      —g          t / \      , / =< N'x, * / N ,,  ,, <                    b^Vxi rNvVxi   Fvjj-x,    nH ,    ,,, A     j / =\ v             J P'N r / \ s nA Axi      / =< L_z H X,—k    n—      y—N       __ / \    1    Jk A—- /       F3c            !       / /              X-I ,    ,,    , \ N                   n,n ;     / N. pA^'X! An'A^Xi FVNx 1 F3c X, ' J                                   x, ,,,, , ^J=(            LvN=V I_ FAjAXi      Xi         r\ / Xland; X1 is the point of attachment to L or ULM;preferably,is selected from the group consisting of the following structures orXiisomers thereof:attachment to L or ULM;A>- AN ,       N      and         xi ; X1 is the point of(R3)n3preferably,is selected from the group consisting of the following structuresor..                                   No>                   ,N                   I J I             /              / =NmTVx      mn=Vx H / Misomers thereof:             Al ,         y ,                , s               and        N ; X1 isthe point of attachment to L or ULM;(R3)n310preferably,is selected from the group consisting of the following structuresorisomers thereof:rA Axiand     '' N     ; X1 is the point ofattachment to L or ULM;(R3)n3preferably,is selected from the group consisting of the following structures or isomersM\ / Ax! rA / Axithereof:     —J     and       N     ; X1 is the point of attachment to L or ULM.15        17. The compound of formula (I) according to claim 2, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein POI is selected from the group consisting of the followingstructures or isomers thereof:andwherein X1 is the point of attachment to L or ULM;preferably, POI is selected from the group consisting of the following structures or isomersthereof:and;preferably, POI is selected from the group consisting of the following structures or isomersthereof:and; wherein X1 is the point of attachment to L or ULM;preferably, POI is selected from the group consisting of the following structures or isomersthereof:andwherein X1 is the point of attachment to L or ULM;preferably, POI is selected from the group consisting of the following structures or isomerswherein X1 is the point of attachment to L or ULM.

18. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein L is a structure of formula (L-1) or an isomer thereof,-(La)m1-(L-1),wherein m1 is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;each La at each occurrence is independently selected from the group consisting of a chemical bond, -C(O)-, -C(O)NRL1-, -NRL1-, -O-, -S-, C1-10 alkylene (preferably C1-8 alkylene, more preferably C1-6 alkylene, further preferably C1-3 alkylene), C1-10 alkyleneoxy (preferably C1-8 alkyleneoxy, more preferably C1-6 alkyleneoxy, further preferably C1-3 alkyleneoxy), C2-10 alkenylene (preferably C2-8 alkenylene, more preferably C2-6 alkenylene, further preferably C2-4 alkenylene), C2-10 alkynylene (preferably C2-8 alkynylene, more preferably C2-6 alkynylene, further preferably C2-4 alkynylene), a C3-15 cycloalkylene ring (preferably a C3-10 cycloalkylene ring, more preferably a C3-8 cycloalkylene ring, further preferably a C3-6 cycloalkylene ring), a 3- to 15-membered heterocycloalkylene ring (preferably a 4- to 12-membered heterocycloalkylene ring, more preferably a 4- to 10-membered heterocycloalkylene ring, further preferably a 4- to 8-membered heterocycloalkylene ring, further preferably a 4- to 6-membered heterocycloalkylene ring), a 5- to 15-membered heteroarylene ring (preferably a 5- to 14-membered heteroarylene ring, more preferably a 5- to 12-membered heteroarylene ring, further preferably a 5- to 10-membered heteroarylene ring, further preferably a 5-to 6-membered heteroarylene ring) and a C6-14 arylene ring (preferably a phenylene ring or a naphthylene ring); the C1-10 alkylene, C1-10 alkyleneoxy, C2-10 alkenylene, C2-10 alkynylene, C3-15 cycloalkylene ring, 3- to 15-membered heterocycloalkylene ring, 5- to 15-membered heteroarylene ring and C6-14 arylene ring are unsubstituted or substituted with 1, 2, 3 or 4 RL2, each RL2 is independently selected from the group consisting of deuterium, halogen (preferably fluorine, chlorine or bromine), hydroxyl, cyano, amino, carboxyl, formyl, oxo, sulfo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy-substituted C1-6 alkyl, cyano-substituted C1-6 alkyl,amino-substituted C1-6 alkyl, C1-6 alkoxy C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl C1-6 alkyl, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl C1-6 alkyl, 5- to 6-membered heteroaryl, 5- to 6-membered heteroaryl C1-6 alkyl, phenyl, phenyl C1-6 alkyl, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -SO2NH2, -SO2NHC1-6 alkyl and -SO2N(C1-6 alkyl)2;each RL1 at each occurrence is independently selected from the group consisting of hydrogen, deuterium, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy) and C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl).

19. The compound of formula (I) according to claim 18, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each RL1 at each occurrence is independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, trifluoroethyl, difluoroethyl, monofluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, trifluoroethoxy, difluoroethoxy and monofluoroethoxy;preferably, each RL1 at each occurrence is independently selected from the group consisting of hydrogen, methyl, ethyl, difluoromethyl and monofluoromethyl;preferably, RL1 is hydrogen.

20. The compound of formula (I) according to claim 18, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each RL2 is independently selected from the group consisting of deuterium, halogen (preferably fluorine, chlorine or bromine), hydroxyl, cyano, amino, carboxyl, hydroxymethyl, hydroxyethyl, methyl, ethyl, difluoromethyl, monofluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cyclopentenyl, tetrahydropyrrolyl, tetrahydrofuranyl, phenyl, pyrrolyl, furanyl, thienyl, thiazolyl, oxazolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl,      -CH2-cyclohexenyl,      -CH2-cyclopentenyl,      -CH2-tetrahydropyrrolyl,-CH2-tetrahydrofuranyl, -CH2-phenyl, -CH2-pyrrolyl, -CH2-triazolyl, -CH2-tetrazolyl, -CH2-pyridyl, -CH2-pyrazinyl,   -CH2-triazinyl, methoxy, ethoxy, difluoromethoxy, monofluoromethoxy,trifluoromethoxy, acetyl, acetamido and sulfonamido;preferably, each RL2 is independently selected from the group consisting of deuterium, -F, -Cl, -Br, -OH, -CN, -CHO, -COOH, -NH2, -CH2OH, -CH2CH2OH, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -OCH3, -OCH2CH3, -OCH2F, -OCHF2, -OCF3, -OCH2CH2F,-OCH2CHF2, -OCH2CF3, -COCH3, -CH2-cyclopropyl, cyclopropyl, -CONH2, -COOCH3, -OCOCH3, -CONHCH3, -CON(CH3)2, -SOCH3, -SO2CH3, -SO2NH2, -SO2NHCH3 and -SO2N(CH3)2;preferably, each RL2 is independently selected from the group consisting of deuterium, -F, -Cl, -Br, -OH, -CN, -COOH, -NH2, -CH2OH, -CH2CH2OH, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3,-CH2CH2F, -CH2CHF2, -CH2CF3, -OCH3, -OCH2CH3, -OCH2F, -OCHF2, -OCF3, -OCH2CH2F,-OCH2CHF2, -OCH2CF3, -COCH3, -CH2-cyclopropyl, cyclopropyl and -CONH2;preferably, each RL2 is independently selected from the group consisting of fluorine, chlorine, bromine, hydroxyl and hydroxymethyl.

21. The compound of formula (I) according to claim 18, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each La is independently selected from the group consisting of the following structures or isomers thereof: -C(O)-, -C(O)NH-, -O-, -S-, -NH-, C1-10 alkylene, C1-10 alkyleneoxy, a C3-12 cycloalkylene ring, a 4- to 12-membered heterocycloalkylene ring, a 5- to 6-membered heteroarylene ring and a phenylene ring; the C3-12 cycloalkylene ring, 4- to 12-membered heterocycloalkylene ring, 5- to 6-membered heteroarylene ring and phenylene ring are unsubstituted or substituted with 1, 2, 3 or 4 RL2, and RL2 is selected from the group consisting of fluorine, hydroxyl and hydroxymethyl;preferably, each La is independently selected from the group consisting of the following structures or isomers thereof: -O-, -S-, -NH-, -C(O)-, -C(O)NH-, -(CH2)m2-, -O(CH2)m2-, -(CH2)m2O-, and a divalent form of a cyclic group selected from the group consisting of: a cyclopropane ring, a cyclobutane ring, a bicyclopentane ring, a cyclopentane ring, a cyclohexane ring, an azetidine ring, a tetrahydropyrrole ring, a piperidine ring, a piperazine ring, a hydroxy-substituted piperidine ring, a hydroxy-substituted piperazine ring, a hydroxymethyl-substituted piperidine ring, a hydroxymethyl-substituted piperazine ring, 3,3,5,5-tetramethylpiperidine, 3,3-difluoropiperidine, a 2-azaspiro[3.3]heptane ring, a 6-azaspiro[3.4]octane ring, a 7-azaspiro[3.5]nonane ring, a 2,6-diazaspiro[3.3]heptane ring, a 2,6-diazaspiro[3.4]octane ring, a 2,7-diazaspiro[3.5]nonane ring, a 2-azaspiro[3.5]nonane ring, a spiro[3.3]heptane ring, a spiro[3.4]octane ring, a spiro[3.5]nonane ring, 3,9-diazaspiro[5.5]undecane, a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, a triazine ring, a thiophene ring, a furan ring, a pyrrole ring, a thiazole ring, an oxazole ring, a pyrazole ring, an imidazole ring and a triazole ring; wherein each m2 at each occurrence is independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;preferably, each La is independently selected from the group consisting of the following structures or isomers thereof: -(CH2)-, -(CH2)2-, -(CH2)5-, -C(O)-, -(CH2)3-, -C(O)NH-, -(CH2)8-, -O-, -NH-,andpreferably, each La is independently selected from the group consisting of the following structuresor isomers thereof: -(CH2)-,22. The compound of formula (I) according to claim 18, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein L is selected from the group consisting of the following structures or isomers thereof: -(CH2)m3-, -C(O)-(CH2)m3-, -C(O)NH-(CH2)m3-, -C(O)NH-(CH2)m3-O-, -Cy0-, -NH-Cy0-, -Cy0-NH-(CH2)m3-, -Cy0-(CH2)m3-NH-, -Cy0-(CH2)m3-O-, -C(O)NH-Cy0-, -(CH2)m3-C(O)NH-(CH2)m3-O-Cy0-O-(CH2)m3-,     -Cy0-Cy0-,     -(CH2)m3-Cy0-O-Cy0-O-(CH2)m3-,-Cy0-C(O)NH-Cy0-, -Cy0-(CH2)m3-Cy0-, -Cy0-O-Cy0-, -Cy0-C(O)-Cy0-, -(CH2)m3-Cy0-Cy0 and -C(O)NH-(CH2)m3-Cy0-(CH2)m3-Cy0; wherein each m3 at each occurrence is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each Cy0 at each occurrence is independently selected from the group consisting of a C3-12 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring), a 3- to 12-membered heterocycloalkyl ring (preferably a 3- to 10-membered heterocycloalkyl ring, more preferably a 3- to 8-membered heterocycloalkyl ring, further preferably a 3- to 6-membered heterocycloalkyl ring), a 5- to 6-membered heteroaryl ring and a benzene ring; the C3-12 cycloalkyl ring, 3- to 12-membered heterocycloalkyl ring, 5- to 6-membered heteroaryl ring, benzene ring are unsubstituted or substituted with 1, 2, 3 or 4 RL2, each RL2 at each occurrence is independently selected from the group consisting of deuterium, halogen, hydroxyl, cyano, amino, carboxyl, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, C1-3 haloalkoxy, hydroxy-substituted C1-3 alkyl, cyano-substituted C1-3 alkyl, amino-substituted C1-3 alkyl, C1-3 alkoxy C1-3 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl C1-3 alkyl, -COC1-3 alkyl, -COOC1-3 alkyl, -OCOC1-3 alkyl, -CONH2, -CONHC1-3 alkyl and -CON(C1-3 alkyl)2;preferably, each Cy0 is independently selected from the group consisting of a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a bicyclopentane ring, a cyclohexane ring, an azetidine ring, a hydroxy-substituted azetidine ring, a tetrahydropyrrole ring, a piperidine ring, a hydroxy-substituted piperidine ring, a hydroxymethyl-substituted piperidine ring, a 4-fluoropiperidine ring, 3,3-difluoropiperidine, 3,3,5,5-tetramethylpiperidine, a piperazine ring, a 2-azaspiro[3.3]heptane ring, a 6-azaspiro[3.4]octane ring, a 7-azaspiro[3.5]nonane ring, a 2,6-diazaspiro[3.3]heptane ring, a 2,6-diazaspiro[3.4]octane ring, a 2,7-diazaspiro[3.5]nonane ring, a 2-azaspiro[3.5]nonane ring, a spiro[3.3]heptane ring, a spiro[3.4]octane ring, a spiro[3.5]nonane ring, 3,9-diazaspiro[5.5]undecane, a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, a triazine ring, a thiophene ring, a furan ring, a pyrrole ring, a thiazole ring, an oxazole ring, a pyrazole ring, an imidazole ring and a triazole ring;preferably, each Cy0 is independently selected from the group consisting of a cyclobutane ring, a bicyclopentane ring, a benzene ring, an azetidine ring, a piperidine ring, a piperazine ring and 3,9-diazaspiro[5.5]undecane;preferably, each Cy0 is independently selected from the group consisting of a cyclobutane ring, an azetidine ring, a benzene ring and a piperidine ring;preferably, each Cy0 is independently selected from the group consisting of the followingstructures or isomers thereof:I——I     k / V XN—I■  \= /  ’ and *                *;preferably, each Cy0 is independently selected from the group consisting of the followingstructures or isomers thereof:hohand23. The compound of formula (I) according to claim 18, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein L is selected from the group consisting of the following1015structures or isomers thereof:   xuq / xoc:oand; wherein X00 is a point ofattachment of L to ULM or POI;preferably, L is selected from the group consisting of the following structures or isomers thereof:9        Xoo             H1 /      / /                Aoo IN           AooXqo N'^s)^                    IIH          and     o             ; wherein X00 isthe point of attachment of L to ULM or POI;5        preferably, L is selected from the group consisting of the following structures or isomers thereof:Xoo-N N-Xoowherein X00 is the point of attachment of L to ULM or POI;preferably, L is selected from the group consisting of the following structures or isomers thereof:10and 0           ; wherein X00 is the point of attachment of L to ULM or POI;preferably, L is selected from the group consisting of the following structures or isomers thereof:and; wherein X00 is the point of15attachment of L to ULM or POI;preferably, L is selected from the group consisting of the following structures or isomers thereof:oFand; wherein X10 is a point of attachment of L to POI, and X20 isa point of attachment of L to ULM;10preferably, L is selected from the group consisting of the following structures or isomers thereof:andwherein X10 is thepoint of attachment of L to POI, and X20 is the point of attachment of L to ULM;preferably, L is selected from the group consisting of the following structures or isomers thereof:150and o            ; whereinX10 is the point of attachment of L to POI, and X20 is the point of attachment of L to ULM;preferably, L is selected from the group consisting of the following structures or isomers thereof:_(r) xX2o / ^^^X20          / 2~7Y             Xl0'N*Wxw             HHXwyN and oX20; wherein X10 is the point ofattachment of L to POI, and X20 is the point of attachment of L to ULM;preferably, L is selected from the group consisting of the following structures or isomers thereof:X10-N   N—X20wherein X10 is the point of attachment of L to POI, and X20 is the point ofattachment of L to ULM;preferably, L is selected from the group consisting of the following structures or isomers thereof:and 0           ; wherein X10 is the point of attachment of L to POI, andX20 is the point of attachment of L to ULM;preferably, L is selected from the group consisting of the following structures or isomers thereof:Xl0'N^l ^N'X20     ^N^^N^N-X20' N        and      f F        ; wherein X10 is the point of attachmentof L to POI, and X20 is the point of attachment of L to ULM.

24. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein ULM is a compound of formula (U-1) or an isomer thereof:(^Bl)bF / Uo--Sg c ^3^5 —S4 (RB2)b2(U-l)wherein,------represents         (double bond) or ------ (single bond);U0 is a chemical bond, -N(RU0)-, -CON(RU0)-, -CH2- or -(CH2)2-;each RU0 at each occurrence is independently hydrogen or C1-3 alkyl;ring B is absent or is selected from the group consisting of a 5- to 15-membered heteroaryl ring (preferably a 6- to 12-membered heteroaryl ring, more preferably a 6- to 10-membered heteroaryl ring), a 3- to 15-membered heterocycloalkyl ring (preferably a 5- to 12-membered heterocycloalkyl ring, more preferably a 5- to 10-membered heterocycloalkyl ring), a C3-15 cycloalkyl ring and a C6-10aryl ring (preferably a benzene ring);S1, S3 and S5 are each independently selected from the group consisting of a chemical bond, -O-, -NH-, -N-, -CH2-, -CH-, -C(O)-, -C(O)O-, -C(O)S-, -CH2C(O)-, -CH2C(S)-, -C(S)-, -CONH-, -CH=N-, -N=N-, -CH=CH-, -SO- and -SO2-;S2 and S4 are each independently selected from the group consisting of -N-, -NH-, -CH- and -CH2-;S6 is selected from the group consisting of C, -CH- and N;(RB1)b1 represents substitution of hydrogen on ring B by b1 RB1, b1 is 0, 1, 2 or 3, each RB1 is identical or different, and each RB1 is independently selected from the group consisting of X2, deuterium, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl, hydroxyl, nitro, -NRa1Rb1, C1-8 alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl), C1-8 alkoxy (preferably C1-6 alkoxy, more preferably C1-3 alkoxy), -SC1-8 alkyl (preferably -SC1-6 alkyl, more preferably -SC1-3 alkyl), -SOC1-8 alkyl (preferably -SOC1-6 alkyl, more preferably -SOC1-3 alkyl), -SO2C1-8 alkyl (preferably -SO2C1-6 alkyl, more preferably -SO2C1-3 alkyl), C1-8 haloalkyl (preferably C1-6 haloalkyl, more preferably C1-3 haloalkyl), C1-8 haloalkoxy (preferably C1-6 haloalkoxy, more preferably C1-3 haloalkoxy), amino-substituted C1-8 alkyl (preferably amino-substituted C1-6 alkyl, more preferably amino-substituted C1-3 alkyl), cyano-substituted C1-8 alkyl (preferably cyano-substituted C1-6 alkyl, more preferably cyano-substituted C1-3 alkyl), hydroxy-substituted C1-8 alkyl (preferably hydroxy-substituted C1-6 alkyl, more preferably hydroxy-substituted C1-3 alkyl), carboxy-substituted C1-8 alkyl (preferably carboxy-substituted C1-6 alkyl, more preferably carboxy-substituted C1-3 alkyl), -COC1-8 alkyl (preferably -COC1-6 alkyl, more preferably -COC1-3 alkyl), -COOC1-8 alkyl-CONRa2Rb2 (preferably -COOC1-6 alkyl-CONRa2Rb2, more preferably -COOC1-3 alkyl-CONRa2Rb2), -SO2NRa2Rb2, a C3-15 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring), a 3- to 15-membered heterocycloalkyl ring (preferably a 4- to 12-membered heterocycloalkyl ring, more preferably a 4- to 10-membered heterocycloalkyl ring, further preferably a 4- to 8-membered heterocycloalkyl ring, further preferably a 4- to 6-membered heterocycloalkyl ring), a 5- to 10-membered heteroaryl ring (preferably a 5- to 6-membered heteroaryl ring) and a C6-10 aryl ring (preferably a benzene ring or naphthalene ring); or two adjacent RB1 and carbon atom linked to the two adjacent RB1 together form a C3-15 cycloalkyl ring (preferably a C3-10 cycloalkyl ring, more preferably a C3-8 cycloalkyl ring, further preferably a C3-6 cycloalkyl ring), a 3-to 15-membered heterocycloalkyl ring (preferably a 4- to 12-membered heterocycloalkyl ring, more preferably a 4- to 10-membered heterocycloalkyl ring, further preferably a 4- to 8-membered heterocycloalkyl ring, further preferably a 4- to 6-membered heterocycloalkyl ring), a 5- to 6-membered heteroaryl ring or a benzene ring; the C3-15 cycloalkyl ring, 3- to 15-membered heterocycloalkyl ring, 5- to 6-membered heteroaryl ring or benzene ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of: X2, deuterium, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl, hydroxyl, nitro, -NRa1Rb1, C1-6 alkyl, C1-6 alkoxy, -SC1-6 alkyl, -SOC1-6 alkyl, -SO2C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, -COC1-6 alkyl, -COOC1-6alkyl, -CONRa2Rb2 and -SO2NRa2Rb2;(RB2)b2 represents substitution of hydrogen on ring C by b2 RB2, b2 is 0, 1, 2, 3 or 4, each RB2 is identical or different, and each RB2 is independently selected from the group consisting of X2, deuterium, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl, hydroxyl, -NRa1Rb1, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONRa2Rb2, -OC(O)C1-6 alkyl-substituted C1-6 alkyl and -COOC1-6 alkyl-substituted C1-6 alkyl;Ra1, Rb1, Ra2 and Rb2 are each independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, hydroxy-substituted C1-6 alkyl, cyano-substituted C1-6 alkyl, carboxy-substituted C1-6 alkyl, amino-substituted C1-6 alkyl, -COC1-6 alkyl and -COOC1-6 alkyl;X2 in RB1 and RB2 is a point of attachment of ULM to L or POI, and at least one of RB1 and RB2 is X2.

25. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RB1 and RB2 are not both X2.

26. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein ring B is absent;or the 5- to 15-membered heteroaryl ring in ring B is selected from the group consisting of a pyrrole ring, a furan ring, a thiophene ring, a pyrazole ring, an imidazole ring, a triazole ring, a tetrazole ring, an oxazole ring, a thiazole ring, an oxadiazole ring, a thiadiazole ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a triazine ring, a benzopyrrole ring, a benzofuran ring, a benzothiophene ring, a benzopyrazole ring, a benzimidazole ring, a benzothiazole ring, a benzoxazole ring, a pyridopyrrole ring, a pyridofuran ring, a pyridothiophene ring, a pyridopyrazole ring, a pyridoimidazole ring, a pyridothiazole ring, a pyridooxazole ring, a pyrimidopyrrole ring, a pyridazopyrrole ring, a pyrazinopyrrole ring, a pyrimidopyrazole ring, a pyridazopyrazole ring, a pyrazinopyrazole ring, a pyrimidoimidazole ring, a pyridazoimidazole ring, a pyrazinoimidazole ring, a quinoline ring, an isoquinoline ring and a 9H-pyrido[2,3-b]indole ring;preferably, the 5- to 15-membered heteroaryl ring in ring B is a benzopyrazole ring; / ^4      eII°2\or the 3- to 15-membered heterocycloalkyl ring in ring B is Qi     8    , wherein Q1, Q2, Q3,Q4 are each independently selected from the group consisting of -CH-, N and N-O;S7 and S8 are each independently selected from the group consisting of a chemical bond, -O-, -NH-, -CH2-, -C(O)-, -C(O)O-, -C(O)S-, -CH2C(O)-, -CH2C(S)-, -C(S)-, -CONH-, -CH=N-, -N=N-, -CH=CH-, -SO- and -SO2-;represents a covalent connection to U0;preferably, Q1, Q2, Q3 and Q4 are each independently -CH-;preferably, S7 and S8 are each independently selected from the group consisting of -CH2- and -C(O)-;preferably, S7 is -CH2-, and S8 is -C(O)-;preferably, S7 is -C(O)-, and S8 is -C(O)-;preferably,is selected from the group consisting of the following structures orisomers thereof:o )=°Nand             ; whereinrepresents a covalent connection to U0;Cbi / ®9( B2 F--S10or the 3- to 15-membered heterocycloalkyl ring in ring B is              , wherein ring B1 andring B2 are each independently selected from the group consisting of a C4-8 cycloalkyl ring, a 4- to 8-membered heterocycloalkyl ring, a 5- to 6-membered heteroaryl ring and a benzene ring; S9 and S10 are each independently selected from the group consisting of a bond, -CH2- and -C(O)-; represents a covalent connection to U0;U0;preferably,isandselected from the group consisting of; whereinor the 3- to 15-membered heterocycloalkyl ring in ring B isrepresents a covalent connection to; wherein ring B3 is a3- to 7-membered heterocycloalkyl ring, and         represents the covalent connection to U0;preferably, ring B3 is a 5- to 7-membered nitrogen-containing heterocycloalkyl ring;preferably, ring B3 is a partially unsaturated 5- to 7-membered nitrogen-containing heterocycloalkyl ring;preferably, ring B3 is selected from the group consisting of 2,5-dihydro-1H-pyrrole, 2,3-dihydro-1H-pyrrole,            1,2,3,6-tetrahydropyridine,            1,2,3,4-tetrahydropyridine,2,3,6,7-tetrahydro-1H-azepine, 2,3,4,7-tetrahydro-1H-azepine and 2,3,4,5-tetrahydro-1H-azepine;preferably,is selected from the group consisting ofandoH      o ; wherein ^rx^r- represents the covalent connection to U0.

27. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein ring B is selected from the group consisting of: a benzene10and; whereinrepresents a covalent connection to U0;preferably, ring B is selected from the group consisting of:and; whereinrepresents a covalent connection to U0;preferably, ring B is selected from the group consisting of:and; whereinrepresents the covalent connection to U0.

28. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt15 thereof, or a stereoisomer thereof, wherein each RB1 is independently X2, deuterium, fluorine, chlorine, bromine, cyano, carboxyl, hydroxyl, nitro, -NH2, -N(CH3)2, -NHCH3, -NHCOCH3, methyl, ethyl,propyl, isopropyl, methoxy, ethoxy, isopropoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, -SCH3, -SOCH3, -SO2CH3, -CH2NH2,-(CH2)2NH2, -(CH2)3NH2, -CH2CN, -(CH2)2CN, -(CH2)3CN, -CH2OH, -(CH2)2OH, -(CH2)3OH,-CH2COOH, -(CH2)2COOH, -(CH2)3COOH, -COCH3, -COCH2CH3, -COOCH3, -COOCH2CH3,5   -CONH2 or -SO2NH2; or two adjacent RB1 and carbon atom linked to the two adjacent RB1 togetherform a cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring, a cycloheptyl ring, a cyclopentene ring, a cyclohexene ring, a cycloheptene ring, a tetrahydropyrrole ring, a tetrahydrofuran ring, a tetrahydrothiophene ring, a piperidine ring, a pyrazine ring, a 1,2,3,4-tetrahydropyridine ring, a 1,2,3,4-tetrahydropyran ring, a 3,4-dihydro-2H-1,4-oxazine ring, a 2,3,4,5-tetrahydro-1H-azepine ring, 10 a pyrrole ring, a pyrazole ring, an oxazole ring, a thiazole ring, a pyran ring, a pyridine ring, apyridazine ring, a pyrimidine ring or a benzene ring; the cyclobutyl ring, cyclopentyl ring, cyclohexyl ring, cycloheptyl ring, cyclopentene ring, cyclohexene ring, cycloheptene ring, tetrahydropyrrole ring, tetrahydrofuran ring, tetrahydrothiophene ring, piperidine ring, pyrazine ring, 1,2,3,4-tetrahydropyridine ring, 1,2,3,4-tetrahydropyran ring, 3,4-dihydro-2H-1,4-oxazine ring, 15 2,3,4,5-tetrahydro-1H-azepine ring, pyrrole ring, pyrazole ring, oxazole ring, thiazole ring, pyran ring,pyridine ring, pyridazine ring, pyrimidine ring, or benzene ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of: X2, deuterium, fluorine, chlorine, bromine, cyano, carboxyl, hydroxyl, nitro, amino, methyl, trifluoromethyl, methoxy, trifluoromethoxy, -SCH3, -SOCH3, -SO2CH3, -COCH3, -COOCH3, -CONH2 and -SO2NH2;20        preferably, RB1 is selected from the group consisting of X2, fluorine, chlorine, hydroxyl, methyl,trifluoromethyl and methoxy.

29. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, whereinis selected from the group consistingof:25oand, wherein X2 is the point of attachment of ULM to L or POI, andrepresents acovalent connection to U0;preferably,is selected from the group consisting of:Oo and\n-n10 x2 x-       , wherein x2 is the point of attachment of ULM to L or POI, and         represents thecovalent connection to U0.

30. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein U0 is a chemical bond, -NH-, -CONH- or -CH2-.

31. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt 15 thereof, or a stereoisomer thereof, wherein S1 and S3 are -C(O)-, S2 is -NH-, S4 and S5 are -CH2-.

32. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein S6 is CH or N.

33. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt / Si—S2--S6thereof, or a stereoisomer thereof, wherein       $5  $4 B2 b2 is selected from the group consistingof the following structure or an isomer thereof:      (RB2)t>2  ; wherein         represents a covalentconnection to U0;S-, S2--S6" -^(R )preferably,       $5 S4 t B2tb2 is selected from the group consisting of the following structuresor isomers thereof:whereinrepresents a covalentconnection to U0.1034. The compound of formula (I) according to claim 24, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein ULM is selected from the group consisting of the following15000structures or isomers thereof:x2andH °N0; wherein X2 is the point of attachment of ULM to L or POI;5        preferably, ULM is selected from the group consisting of the following structure or an isomerX2 O Othereof:o           ; wherein X2 is the point of attachment of ULM to L or POI;preferably, ULM is selected from the group consisting of the following structures or isomerso othereof:            o; wherein X2 is the pointof attachment of ULM to L or POI.10        35. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein ULM is a structure of formula (U-2) or an isomer thereof:(U-2),wherein, r1 is 0, 1 or 2;15ring D is selected from the group consisting of a benzene ring, a 5- to 6-membered heteroaryl ring, a C3-10 cycloalkyl ring (preferably a C3-8 cycloalkyl ring, more preferably a C3-6 cycloalkyl ring) and a 3- to 10-membered heterocycloalkyl ring (preferably a 3- to 8-membered heterocycloalkyl ring, more preferably a 3- to 6-membered heterocycloalkyl ring);(RU2)r2 represents substitution of hydrogen on ring D by r2 RU2, r2 is 0, 1, 2 or 3, each RU2 isidentical or different, and each RU2 is independently selected from the group consisting of X2, hydrogen, deuterium, halogen (preferably fluorine, chlorine), nitro, cyano, carboxyl, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy C1-6 alkyl, hydroxy-substituted C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, -NRa3Rb3, -COC1-6 alkyl, -COOC1-6 alkyl, -OCOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CON(C1-6 alkyl)2, -SOC1-6 alkyl, -SO2C1-6 alkyl, -SC1-6 alkyl, 5- to 6-membered heteroaryl and phenyl; the 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, C1-6 alkyl (preferably C1-3 alkyl), hydroxy-substituted C1-6 alkyl (preferably hydroxy-substituted C1-3 alkyl), C1-6 alkoxy C1-6 alkyl (preferably C1-3 alkoxy C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (preferably C1-3 haloalkoxy), -NH2, -NHCOC1-6 alkyl (preferably -NHCOC1-3 alkyl), -COC1-6 alkyl (preferably -COC1-3 alkyl), -COOC1-6 alkyl (preferably -COOC1-3 alkyl), -OCOC1-6 alkyl (preferably -OCOC1-3 alkyl), -CONH2, -NHCONH2, -CONHC1-6 alkyl (preferably -CONHC1-3 alkyl), -NHCONHC1-6 alkyl (preferably -NHCONHC1-3 alkyl), -SOC1-6 alkyl (preferably -SOC1-3 alkyl), -SO2C1-6 alkyl (preferably -SO2C1-3 alkyl) and -SC1-6 alkyl (preferably -SC1-3 alkyl);RU1 is -C(RU3RU4)-U1;U1 is selected from the group consisting of the following structures or isomers thereof: X2,-NHCO-X2, -NHCOCH3,a 5- to 6-membered heteroaryl ring,and, the 5- to 6-membered heteroaryl ring,andare unsubstituted orsubstituted with 1, 2 or 3 substituents selected from the group consisting of: X2, halogen, hydroxyl, cyano, amino, carboxyl, C1-6 alkyl (preferably methyl, ethyl, isopropyl), C1-6 alkoxy (preferably methoxy, ethoxy, isopropoxy), C1-6 haloalkyl (preferably trifluoromethyl), C1-6 haloalkoxy (preferably trifluoromethoxy), -COC1-6 alkyl (preferably -COCH3), -COOC1-6 alkyl (preferably -COOCH3), -CONH2, -CONHC1-6 alkyl (preferably -CONHCH3), -CON(C1-6 alkyl)2 (preferably -CON(CH3)2) and hydroxy-substituted C1-6 alkyl (preferably -CH2OH);RUa is selected from the group consisting of hydrogen, halogen (preferably fluorine, chlorine, or bromine), cyano, hydroxyl, carboxyl, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -COC1-6 alkyl, -NHCOC1-6 alkyl, -N(C1-6 alkyl)COC1-6 alkyl, -NHC1-6 alkyl and -N(C1-6 alkyl)2;preferably, RUa is selected from the group consisting of fluorine, cyano, methyl, ethyl, trifluoromethyl and trifluoromethoxy;preferably, RUa is selected from the group consisting of fluorine and cyano;RU3 and RU4 are each independently selected from the group consisting of hydrogen, deuterium, halogen, cyano, carboxyl, hydroxyl, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), C1-6 haloalkyl (preferably C1-3 alkoxy), C1-6 haloalkoxy (preferably C1-3 haloalkoxy), and-SC1-6 alkyl (preferably -SC1-3 alkyl); or RU3, RU4, and carbon atom linked to RU3 and RU4 together form a C3-7 cycloalkyl (preferably C3-6 cycloalkyl) or a 3- to 7-membered heterocycloalkyl (preferably a 4- to 6-membered heterocycloalkyl); the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -SC1-6 alkyl, C3-7 cycloalkyl and 3- to 7-membered heterocycloalkyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: X2, halogen (preferably fluorine, chlorine or bromine), cyano, carboxyl and hydroxyl;RU5 and RU6 are each independently selected from the group consisting of X2, hydrogen, deuterium, halogen, amino, cyano, carboxyl, hydroxyl, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (C1-3 haloalkoxy), -SC1-6 alkyl (preferably -SC1-3 alkyl), CONHC1-6 alkyl-substituted C1-6 alkyl, CON(C1-6 alkyl)2-substituted C1-6 alkyl, carboxy-substituted C1-6 alkyl and COOC1-6 alkyl-substituted C1-6 alkyl;RU7 is selected from the group consisting of hydrogen, C1-6 alkyl, and C1-6 haloalkyl; or RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a 3- to 8-membered heterocycloalkyl ring or a 5- to 6-membered heteroaryl ring;RU8 is selected from the group consisting of hydroxyl, amino, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C1-6 alkoxy, C1-6 haloalkoxy and -OCOC1-6 alkyl;Ra3 and Rb3 are each independently selected from the group consisting of hydrogen, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), -SC1-6 alkyl (preferably -SC1-3 alkyl), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (preferably C1-3 haloalkoxy), -COC1-6 alkyl (preferably -COC1-3 alkyl), -CONH2, -CONHC1-6 alkyl (preferably -CONHC1-3 alkyl), -CON(C1-6 alkyl)2 (preferably -CON(C1-3 alkyl)2), 5- to 6-membered heteroaryl and phenyl; wherein the 5- to 6-membered heteroaryl and phenyl are each independently unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: hydrogen, C1-6 alkyl (preferably C1-3 alkyl), C1-6 alkoxy (preferably C1-3 alkoxy), -SC1-6 alkyl (preferably -SC1-3 alkyl), C1-6 haloalkyl (preferably C1-3 haloalkyl), C1-6 haloalkoxy (preferably C1-3 haloalkoxy), -COC1-6 alkyl (preferably -COC1-3 alkyl), -CONH2, -CONHC1-6 alkyl (preferably -CONHC1-3 alkyl) and -CON(C1-6 alkyl)2 (preferably -CON(C1-3 alkyl)2);preferably, Ra3 and Rb3 are each independently selected from the group consisting of hydrogen, 5-to 6-membered heteroaryl, and phenyl; the 5- to 6-membered heteroaryl is thiazolyl, oxazolyl, pyrazolyl, imidazolyl, thienyl, furanyl, pyrrolyl, triazolyl or tetrazolyl; the 5- to 6-membered heteroaryl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of: hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, trifluoromethoxy, -COCH3 and -CONH2;X2 in RU2, RU1, RU5 and RU6 is a point of attachment of ULM to L or POI, and at least one of RU1, RU5, RU6 and RU2 is X2.

36. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein ring D is selected from the group consisting of a benzene ring, a 5- to 6-membered heteroaryl ring, a C5-9 cycloalkyl ring and a 5- to 9-memberedheterocycloalkyl ring;preferably, ring D is selected from the group consisting of a benzene ring and 2,3-dihydro-1H-indene;preferably, ring D is 2,3-dihydro-1H-indene;preferably, ring D is selected from the group consisting of a benzene ring and a 5- to 6-membered heteroaryl ring;preferably, ring D is selected from the group consisting of a benzene ring, a pyrrole ring, a thiophene ring, a furan ring, a pyrazole ring, an imidazole ring, a triazole ring, a thiazole ring, an oxazole ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a piperidine ring, a piperazine ring and a tetrahydropyrrole ring;preferably, ring D is selected from the group consisting of a benzene ring and a pyridine ring;preferably, ring D is a benzene ring.

37. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein r1 is 1, and ring D is a benzene ring.

38. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU2 is 5- to 6-membered heteroaryl or phenyl, the 5- to 6-membered heteroaryl or phenyl is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: deuterium, halogen (preferably fluorine, chlorine), cyano, carboxyl, hydroxyl, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, C1-3 haloalkoxy, -NH2, -NHCOC1-3 alkyl, -COC1-3 alkyl, -COOC1-3 alkyl, -OCOC1-3 alkyl, -CONH2, -NHCONH2, -CONHC1-3 alkyl, -NHCONHC1-3 alkyl, -SOC1-3 alkyl, -SO2C1-3 alkyl and -SC1-3 alkyl;preferably, the 5- to 6-membered heteroaryl is selected from the group consisting of thiazolyl, oxazolyl, pyrazolyl, imidazolyl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, tetrazolyl and triazolyl;H 0—Ipreferably, the 5- to 6-membered heteroaryl is selected from the group consisting of          ,n"A , hn^ / =\          n^n\        / =O'1, ^, CO 01 and ■;preferably, the 5- to 6-membered heteroaryl is s     ;preferably, the 5- to 6-membered heteroaryl is selected from the group consisting of a thiazole ring, an oxazole ring, a pyrazole ring, an imidazole ring, a pyrrole ring, a pyridine ring, a pyrimidine ring, a pyridazine ring, a pyrazine ring, a tetrazole ring and a triazole ring;preferably, RU2 is cyano.

39. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU2 is -NHRa3, wherein Ra3 is 5- to 6-membered heteroaryl or phenyl, the 5- to 6-membered heteroaryl is selected from the group consisting of thiazolyl,imidazolyl, pyrazolyl, oxazolyl, pyridyl and pyrimidinyl; the 5- to 6-membered heteroaryl or phenyl is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of: C1-3 alkoxy, C1-3 haloalkoxy, C1-3 alkyl, C1-3 haloalkyl, -SC1-3 alkyl and -OCOC1-3 alkyl;preferably, RU2 is -NHRa3, wherein Ra3 is thiazolyl; the thiazolyl is substituted with 1, 2 or 3 substituents selected from the group consisting of: methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, monofluoroethoxy, difluoroethoxy and trifluoroethoxy;preferably, RU2 is -NHRa3, wherein Ra3 is thiazolyl; the thiazolyl is substituted with 1, 2, or 3 substituents selected from the group consisting of: methyl, ethyl, propyl and isopropyl.

40. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU2 is selected from the group consisting of the followingn3h                      Thstructures: cyano, s ,         s        , s ,      \    ,     \    ,   /         and "-n    .

41. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable saltIthereof, or a stereoisomer thereof, wherein r2 is 1, and RU2 is s .

42. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein r2 is 2, and RU2 are X2 and, respectively.

43. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable saltattachment of ULM to L or POI;(Ru2)r2—f D J--jpreferably,                      is selected from the group consisting of the following structure— 335 —or an isomer thereof:

44. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein one of RU1, RU5, RU6 and RU2 is X2.

45. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein U1 is selected from the group consisting of X2, -NHCO-X2,-NHCOCH3,oH .and0; wherein X2 is the point of attachment of ULM to L or POI;preferably, U1 is selected from the group consisting of -NHCO-X2 and x2        ; wherein X2 isthe point of attachment of ULM to L or POI.

46. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU3 and RU4 are each independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy or C1-6 haloalkoxy; or RU3, RU4 and carbon atom linked to RU3 and RU4 form a C3-6 cycloalkyl ring;preferably, RU3 and RU4 are each independently hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CF3, -CHF2, -CH2F, -OCH3, -OCH(CH3)2, -OC(CH3)3, -OCF3, -OCHF2, -OCH2F, fluoro-substituted isopropyl or fluoro-substituted tert-butyl; or RU3, RU4 and carbon atom linked to RU3 and RU4 form a cyclopropyl ring, a cyclobutyl ring, a cyclopentyl ring or a cyclohexyl ring;preferably, RU3 and RU4 are each independently hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2 or -C(CH3)3; or RU3, RU4 and carbon atom linked to RU3 and RU4 form a cyclopropyl ring;preferably, RU3 and RU4 are each independently hydrogen, -CH(CH3)2 or -C(CH3)3.

47. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU1 is selected from the group consisting of the followingstructures or isomers thereof:N-0,or POI;; wherein X2 is the point of attachment of ULM to Lpreferably, RU1 is selected from the group consisting of the following structures:N \__ yyy / ; wherein X2 is the point of attachment of ULM to L or POI;X / N' 7preferably, RU1 is selected from the group consisting of the following structure:       H     ;wherein X2 is the point of attachment of ULM to L or POI.

48. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU5 and RU6 are each independently X2, hydrogen, deuterium, halogen, hydroxyl, carboxyl, cyano, amino, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, or C1-3 haloalkoxy; or RU5 and carbon atom on ring D together form a C3-6 cycloalkyl ring; the C3-6 cycloalkyl ring is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of: deuterium, halogen (preferably fluorine, chlorine, or bromine), cyano, carboxyl, hydroxyl, nitro, formyl, sulfo, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C1-6 alkyl, C1-6 alkoxy, -SC1-6 alkyl, -SOC1-6 alkyl, -SO2C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, amino-substituted C1-6 alkyl, cyano-substituted C1-6 alkyl, hydroxy-substituted C1-6 alkyl, carboxy-substituted C1-6 alkyl, -COC1-6 alkyl, -CO2NH2, -CO2NH(C1-6 alkyl), -CO2N(C1-6 alkyl)2, -SO2NH2, -SO2NH(C1-6 alkyl), -SO2N(C1-6 alkyl)2, a C3-8 cycloalkyl ring, a 4- to 10-membered heterocycloalkyl ring, a 5- to 6-membered heteroaryl ring and a benzene ring;preferably, RU5 and RU6 are each independently hydrogen, C1-3 alkyl, or C1-3 haloalkyl;preferably, RU5 and RU6 are each independently hydrogen, -CH3, -OCH3, -CF3, -OCF3, -CHF2, -CH2F, -OCHF2 or -OCH2F;preferably, RU5 and RU6 are each independently hydrogen or -CH3.

49. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein RU7 is selected from the group consisting of hydrogen, methyl, ethyl, monofluoromethyl, difluoromethyl and trifluoromethyl;preferably, RU7 is hydrogen.

50. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU7, nitrogen atom linked to RU7, RU6, and carbon atom linked to RU6 together form a partially unsaturated 3- to 8-membered heterocycloalkyl ring, a 5- to 6-membered heteroaryl ring or a benzene ring;preferably, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a tetrahydropyrrole ring, a pyrazolidine ring, an imidazolidine ring, a piperazine ring, a piperidine ring, a 2,3-dihydro-1H-pyrrole ring, a 2,3-dihydro-1H-pyrazole ring, a pyrrole ring, a pyrazole ring, an imidazole ring, a pyridine ring, a pyrimidine ring or a benzene ring;preferably, RU7, nitrogen atom linked to RU7, RU6 and the carbon atom linked to RU6 together form a 4- to 6-membered heterocycloalkyl ring;preferably, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a 5-membered heterocycloalkyl ring;preferably, RU7, nitrogen atom linked to RU7, RU6 and carbon atom linked to RU6 together form a tetrahydropyrrole ring.

51. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, whereinis selected from the group consistingof the following structures or isomers thereof:X-andsH ; wherein X2 is the point of attachment ofis selected from the group consisting of the following structuresor isomers thereof:             "N ’ and s —  ^N^.

52. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein RU8 is selected from the group consisting of hydroxyl, amino, -NH(C1-3 alkyl), -N(C1-3 alkyl)2, C1-3 alkoxy, C1-3 fluoroalkoxy and -OCOC1-3 alkyl;preferably, RU8 is selected from the group consisting of hydroxyl, amino, -NH(CH3), -N(CH3)2, -OCH3, -OCF3, and -OCOCH3;preferably, RU8 is hydroxyl.

53. The compound of formula (I) according to claim 35, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein ULM is selected from the group consisting of the followingstructures or isomers thereof:wherein X2 is the point of attachment of ULM to L or POI;preferably, ULM is selected from the group consisting of thefollowing structures or isomersthereof:OHx.OH; wherein X2 is the point ofattachment of ULM to L or POI;10        preferably, ULM is selected from the group consisting of the following structures or isomersandthereof:wherein X2 is the point of attachment of ULM to L or POI.

54. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein the compound of formula (I) is a structure of formula (I-A),wherein ring A1, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in claim 2, L, n0 and ULM are as defined in claim 1, and both R2 and R3 are not X1.

55. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the compound of formula (I) is a structure of formula (I-B),(l-B)wherein ring A1, ring A2, R1, n1, R2, n2, R3 and n3 are as defined in claim 2, L, n0 and ULM are as defined in claim 1, and both R2 and R3 are not X1.1056. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the compound of formula (I) is selected from the group consisting of the following structures or isomers thereof:15wherein ring A2, R1, n1, R2, n2, R3 and n3 are as defined in claim 2, L, n0 and ULM are as defined in claim 1, and both R2 and R3 are not X1.

57. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable saltthereof, or a stereoisomer thereof, wherein the compound of formula (I) is selected from the groupconsisting of the following structures or isomers thereof:(L)„o-ULM(L)no-ULMCNCN(L)n0-ULM(LWULM(L)„o-ULM(L)„o-ULMClN-(L)n0-ULM(L)n0-ULM(L)no-ULM(L)n0-ULM(L)n0-ULM(LWULM(LWULM(L)„0-ULMpreferably, the compound of formula (I) is selected from the group consisting of the followingstructures or isomers thereof:(L)no-ULMandpreferably, the compound of formula (I) is selected from the group consisting of the followingstructures or isomers thereof:(L)„0-ULM(L)„o-ULMand58. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the compound of formula (I) is a compound selected from the group consisting of Table A or a stereoisomer thereof.

59. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the compound of formula (I) is a compound selected from the group consisting of Table B or a stereoisomer thereof.

60. A pharmaceutical composition, comprising the compound of formula (I) according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof; and a pharmaceutically acceptable carrier.

61. Use of the compound of formula (I) according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or the pharmaceutical composition according to claim 60, in the manufacture of a medicament for preventing and / or treating an EED-mediated disease;preferably, the EED-mediated disease is a tumor or an autoimmune disease;preferably, the EED-mediated disease is cancer;preferably, the cancer is selected from the group consisting of multiple myeloma, leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.

62. A method for preventing and / or treating an EED-mediated disease, comprising administering a therapeutically effective amount of the compound of formula (I) according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or the pharmaceutical composition according to claim 60 to a subject;preferably, the EED-mediated disease is a tumor or an autoimmune disease;preferably, the EED-mediated disease is cancer;preferably, the cancer is selected from the group consisting of multiple myeloma, leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.

Images