Compound as voltage-gated sodium channel inhibitor and use thereof

Abstract

The present invention relates to a voltage-gated sodium channel Nav1.8 selective inhibitor and the use thereof in the preparation of a related drug. The drug is used for treating diseases responsive to the inhibition of voltage-gated sodium channel NaV1.8, such as chronic pain, enterodynia, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia. Specifically, the present invention relates to a compound as shown in formula (X), and an isomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug thereof.

Description

The present application claims the right of priority for: CN 202410483482.4, filed on 19 April 2024; and CN 202411125232.X, filed on 15 August 2024. Technical Field The present invention relates to the technical field of chemical and pharmaceutical, and specifically to a compound as a voltage-gated sodium channel inhibitor and the use thereof. Background Art Pain plays an indispensable protective role in the normal vital activities of the body. As a warning signal, it alerts the body to potential dangers. However, pain is also a common clinical symptom. After the external stimulus that triggers the pain disappears, intense or persistent pain can lead to the disruption of physiological functions, seriously affecting the quality of life of living organisms. Pain originates from nociceptors of the peripheral nervous system, which are free nerve endings widely distributed throughout the skin, muscles, joints, and visceral tissues of the body. The nociceptors can convert the thermal, mechanical or chemical stimuli they sense into nerve impulses (action potentials) and transmit the nerve impulses via afferent nerve fibres to their cell bodies located in the dorsal root ganglia (DRG), and ultimately to higher nerve centres, evoking the perception of pain. The generation and conduction of action potentials in neurons in turn depend on voltage-gated sodium ion channels (NaV) on the cell membrane. When the cell membrane depolarises, sodium ion channels are activated and open, causing sodium ion influx, which further depolarises the cell membrane and leads to the generation of action potentials. Therefore, inhibition of aberrant sodium ion channel activity is beneficial for the treatment and alleviation of pain. NaV1.8 is predominantly expressed in the sensory ganglia of the peripheral nervous system, such as the dorsal root ganglion (DRG). Small DRG neurons expressing NaV1.8 include nociceptors involved in pain signalling. NaV1.8 mediates large-amplitude action potentials in small neurons of the dorsal root ganglion and is essential for rapid repetitive action potentials in nociceptors and for the spontaneous activity of damaged neurons. Knockdown of NaV1.8 in rats has been achieved using antisense DNA or small interfering RNA, and has resulted in an almost complete reversal of neuropathic pain in spinal nerve ligation and chronic constriction injury models. Therefore, the NaV1.8 channel is considered a promising target for analgesics and is expected to exert effects in indications where pain outlasts its usefulness, such as neuropathic pain, inflammatory pain, and postoperative / spontaneous pain. Moreover, since NaV1.8 is mainly restricted to pain-sensing neurons, selective NaV1.8 inhibitors may avoid the adverse events commonly associated with non-selective NaV blockers . In addition to pain, the NaV1.8 channel is also believed to be associated with diseases such as multiple sclerosis, arrhythmia, cough, and pruritus. Multiple sclerosis is an inflammatory demyelination disease originating in the central nervous system, and its exact pathogenesis remains to be elucidated. NaV1.8 channels are not expressed in cerebellar Purkinje fibres of healthy individuals, whereas NaV1.8 expression is upregulated in the cerebellum of patients with multiple sclerosis. In the cardiovascular system, NaV1.8 has been shown to be expressed in cardiac nerves such as Purkinje fibres and is considered a potential therapeutic target for cardiovascular diseases such as arrhythmia. NaV1.8 is expressed in the vagal nerve plexus associated with cough, and its phosphorylation level and expression are elevated during pathological cough, thereby contributing to the cough reflex. In the mammalian perception of itch, pruritogens such as histamine released from lymphocytes, mast cells, and other cells can activate the NaV1.8 channel, and knockout of NaV1.8 in mice can effectively alleviate scratching behaviour induced by histamine and endothelin. Currently, the NaV1.8 selective inhibitors VX-150 and Suzetrigine from VERTEX have achieved positive results in clinical trials in patients with acute pain, diabetic peripheral neuropathic pain, etc. However, no product targeting NaV1.8 has been approved to date. Therefore, the development of highly selective voltage-gated sodium channel NaV1.8 inhibitors is of great clinical significance. Summary of the Invention The present invention provides a compound, or a pharmaceutical composition thereof, which can serve as a NaV1.8 selective inhibitor. The present invention further relates to the use of the compound or the pharmaceutical composition thereof in the preparation of a drug, wherein the drug is for use in treating a disease and / or condition by inhibiting NaV1.8 with the compound. The present invention still further describes a method for synthesising the compound. The compounds of the present invention exhibit excellent biological activity and pharmacokinetic properties. Specifically, in one aspect, disclosed is a compound, which is a compound as shown in formula (X), or a stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in formula (X), (X) wherein ring A is phenyl, 5- to 10-membered heteroaryl or 5- to 10-membered heterocyclyl; each Re is independently D, F, Cl, Br, I, CN, hydroxyl, nitro, -N(Ra)2, -(C1-6 alkylene) N(Ra)2,  -S(O)(=NH) C1-6 alkyl, -C(O)ORa, -C(O)N(Ra)2,  -(C1-6 N(Ra)2 4A alkylene)C(O)N(Ra)2, -C(O)Ra, -S(O)2NRa,    N-Ra , c^ alkyl, alkoxy, Cw hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylthio, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkylene, C1-6 alkyl, c1-6 alkoxy, c1-6 hydroxyalkyl, c1-6 haloalkyl, c1-6 haloalkoxy, c1-6 alkylamino, c1-6 alkylthio, c3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, cl, Br, I, cN, hydroxyl, amino, nitro, oxo, hydroxyl, c1-3 alkyl, c1-3 alkylamino, c1-3 haloalkyl, c1-3 hydroxyalkyl and c1-3 alkoxy; each Ra is independently H, D, hydroxyl, c1-6 alkyl, c1-6 alkoxy, c3-6 cycloalkyl and 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, c1-6 alkoxy, c3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, oxo and C1-3 alkyl; R1, R2, R3, R4 and R5 are each independently H, D, F, Cl, Br, I, CN, hydroxyl, nitro, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, nitro, amino, hydroxyl, C1-3 alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl and C1-3 alkoxy; or R3 and R5, together with the carbon atom to which they are attached, form C3-6 cycloalkyl; R6 is CN, -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, -CH=N-O-C1-6 alkyl, C2-6 alkynyl, C1-6 alkylthio or -L1-L2-Rc, wherein the C1-6 alkyl, C2-6 alkynyl and C1-6 alkylthio may be independently and optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, oxo and hydroxyl; L1 is a bond, O or S; L2 is a bond, C1-6 alkylene or -(C1-6 alkylene)-C1-6 alkoxy, wherein the C1-6 alkylene and C1-6 alkoxy may be independently and optionally substituted with 1 or 3 substituents selected from D, F, Cl, Br, I, oxo and hydroxyl; Rc is -O-N=, -P(O)(C1-6 alkyl)2, C2-6 alkynyl or -O-(3- to 8-membered heterocyclyl), wherein the C1-6 alkyl, C2-6 alkynyl and 3- to 8-membered heterocyclyl may be independently and optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from D, F, Cl, Br, I, hydroxyl, oxo, nitro, amino, alkylamino, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl; R7 and R8 are each independently H, D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, hydroxyl, amino, nitro and C1-3 alkoxy; n is 0, 1, 2 or 3; ring A may be phenyl, pyridazine, pyrazine, pyridine or pyrimidine. In some embodiments, the compound is a compound as shown in formula (I), (II) or (III), or a stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in formula (I), (II) or (III), wherein (I), (II), (III) X is CR10 or N; Y is CR13 or N; R9 and R10 are each independently H, D, F, Cl, Br, I, CN, amino, nitro, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl or C1-6 haloalkoxy; R11, R12 and R13 are each independently H, D, F, Cl, Br, I, CN, hydroxyl, nitro, -N(Ra)2, -(C1-6 alkylene) N(Ra)2, -S(O)(=NH) C1-6 alkyl, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2 -V4 , (C1-6 alkylene)C(O)N(Ra)2, -C(O)Ra, -S(O)2NRa,    N-Ra , cw alkyl, cw alkoxy, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylthio, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkylene, C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylthio, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, oxo, hydroxyl, C1-3 alkyl, C1-3 alkylamino, C1-3 haloalkyl, C1-3 hydroxyalkyl and C1-3 alkoxy; each Ra is independently H, D, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, oxo and C1-3 alkyl. In some embodiments, R1, R2, R3, R4 and R5 are each independently H, D, F, Cl, Br, I, hydroxyl, methyl, ethyl, CH2F, CHF2, CF3, -CH2OCH3 or -CH2OH. In some embodiments, R9, R10 and R11 are each independently H, D, F, Cl, Br, I, CN, amino, nitro, methyl, ethyl, methoxy, trifluoromethyl or trifluoromethoxy; R12 and R13 are each independently H, D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, methyl, ethyl, CH2F, CHF2, -OCH3, -OCH2 CH3, -C(O)NH2, -C(O)NHOH, -C(O)NHOCH3, - CH2OH, -CH(OH)CH2OH, -C(O)NHCH3, -CH(OH)(CH3)2, - nh2 S(O)(=NH) CH3, -S(O)2NH2,    N-OH or In some embodiments, R7 and R8 are each independently H, D, F, Cl, Br, I, hydroxyl, methyl, ethyl, CH2F, CHF2 or CF3. In some embodiments, R6 is CN, -S(O)C1-3 alkyl -S(O)2C1-3 alkyl, -CH=N-O-C1-3 alkyl, -C2-6 alkynyl, C1-3 alkylthio or -L1-L2-Rc, and the C1-3 alkyl, C1-3 alkylthio and C2-6 alkynyl may be independently and optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, oxo and hydroxyl; L1 is a bond, O or S; L2 is a bond, C1-3 alkylene or -(C1-3 alkylene)- C1-3 alkoxy; Rc is -O-N=, -P(O)(CH3)2, C2-6 alkynyl or -O-(3- to 8-membered heterocyclyl), wherein the C2-6 alkynyl and 3- to 8-membered heterocyclyl may be independently and optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from D, F, Cl, Br, I, hydroxyl, oxo, nitro, amino, C1-3 alkyl, C1-3 alkoxy, C1-3 alkylthio, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl. In some embodiments, R6 is CN, -S(O)CH3, -S(O)2CH3,            , - dd D 0 or In some embodiments, the compound disclosed in the present invention has a 5 structure shown in formula (IV) or (V): wherein Rc is C2-6 alkynyl, and the C2-6 alkynyl may be independently and optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from D, F, Cl, Br, I, hydroxyl, nitro, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C3-6 cycloalkyl and 10   3- to 6-membered heterocyclyl. In some embodiments, the compound is a compound having one of the following structures, or a stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound having one of the following structures: 01 In one aspect, the present invention relates to a pharmaceutical composition comprising the compound as shown in formula (I) or the stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug thereof according to the present invention, and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle, or a combination thereof. In one aspect, the present invention discloses the use of the compound and the pharmaceutical composition in the preparation of a drug for treating a disease responsive to the inhibition of voltage-gated sodium channel NaV1.8, wherein the disease is chronic pain, enterodynia, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia. The foregoing contents merely outline certain aspects of the present invention, but are not limited thereto. The contents of these and other aspects will be described in greater detail and completeness hereinafter. Definitions and general terms The present invention will list in detail the literature corresponding to the specified contents as identified, with examples accompanied by illustrations of structural formulas and chemical formulas. The present invention is intended to cover all alternatives, variations, and equivalents that may be encompassed within the field of the present invention as defined in the claims. Those skilled in the art will recognise many methods and materials similar or equivalent to those described herein, which can be used in the practice of the present invention. The present invention is by no means limited to the description of the methods and materials. There are many literature and similar materials that differ from or contradict the present application, including, but by no means limited to, definitions of terms, usage of terms, described techniques, or the scope as set forth in the present application. The following definitions shall apply to the present invention unless otherwise indicated. For the purposes of the present invention, the chemical elements are defined in accordance with the Periodic Table of the Elements, CAS version and the Handbook of Chemistry and Physics, 75th Ed., 1994. In addition, the general principles of organic chemistry can be found in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March’s Advanced Organic Chemistry" by Michael B. Smith and Jerry March, John Wiley&Sons, New York: 2007, the contents of which are incorporated by reference in their entirety. The term “comprise” is an open-ended expression, encompassing the contents indicated in the present invention without excluding the contents from other aspects. The compounds described herein may be optionally substituted with one or more substituents, such as the compounds of general formulas in the present invention, or specific examples in the embodiments, the subclasses, and classes of compounds encompassed by the present invention. It should be understood that the term "optionally substituted" can be used interchangeably with the term "substituted or unsubstituted". Generally, the term "optionally", whether preceding the term "substituted" or not, means that one or more hydrogen atoms in a given structure are substituted with a specified substituent. Unless otherwise indicated, an optional substituent group may have a substituent at each substitutable position of the group. When more than one position in a given structural formula can be substituted with one or more substituents selected from a particular group, the substituents may be the same or different at each position. The substituents may be, but are not limited to, hydrogen, F, Cl, Br, I, nitro, cyano, oxo (=O), hydroxyl, alkyl, hydroxyalkyl, alkylamino, aminoalkyl, haloalkoxy, cycloalkyl, amino, aryl, heterocyclyl, heteroaryl, alkenyl, alkynyl, cycloalkyloxy, alkoxy, alkoxyalkyl, haloalkyl, -COOH, -alkylene-C(=O)O-alkyl, -alkylene-S(=O)2-alkyl, -alkylene-S(=O)2-amino, -S(=O)2-alkyl, -S(=O)2-amino, -S(=O)2OH, -O-alkylene-C(=O)O-alkyl, -O-alkylene-S(=O)2-alkyl, -O-alkylene-S(=O)2-amino, -O-alkylene-S(=O)2OH, -C(=O)NH2, -C(=O)NH-alkyl, -C(=O)N(alkyl)-alkyl, -C(=O)NHS(=O)2-alkyl, -C(=O)NHS(=O)2-amino, -C(=O)NHS(=O)2OH, -N(haloalkyl)-alkyl, -N(alkyl)-S(=O)2-alkyl, -NHS(=O)2-alkyl, -NHS(=O)2-haloalkyl, -N(alkyl)S(=O)2-haloalkyl, -N(alkyl)S(=O)2-alkylamino, -NHC(=O)-alkyl, -NHC(=O)-haloalkyl, -N(alkyl)C(=O)-haloalkyl, -N(alkyl)C(=O)-alkylamino, -N(alkyl)C(=O)O-alkyl, -NHC(=O)O-alkyl, -NHC(=O)O-haloalkyl, -N(alkyl)C(=O)O-haloalkyl, -N(alkyl)C(=O)O-aminoalkyl,    -NHC(=O)-NH2,    -NHC(=O)NH-(alkyl), - NHC(=O)NH(haloalkyl), -NHC(=O)N(alkyl)-alkyl, -OC(=O)-alkyl, -OC(=O)- amino, -OC(=O)-alkylamino, -OC(=O)-aminoalkyl, -OC(=O)-alkoxy, -C(=O)N(alkyl)S(=O)2-alkyl, -C(=O)N(alkyl)S(=O)2-amino, -C(=O)NH-S(=O)2OH, -C(=NH)NH2, -C(=NH)NH-alkyl, -C(=NH)N(alkyl)-alkyl, -C(=N-alkyl)-NH2, -C(=O)NH-alkylene-S(=O)2OH, -C(=O)NHC(=O)OH, -C(=O)NHC(=O)O-alkyl, -C(=O)N(alkyl)C(=O)O-alkyl, -C(=O)NH-alkylene-C(=O)OH, -C(=O)NH-alkylene-C(=O)O-alkyl, etc. The term “alkyl” as used in the present invention refers to a saturated linear or branched monovalent hydrocarbon group having 1-20 carbon atoms, or 1-10 carbon atoms, or 1-6 carbon atoms, or 1-4 carbon atoms, or 1-3 carbon atoms, or 1-2 carbon atoms, wherein the alkyl may be independently and optionally substituted with one or more substituents described in the present invention. Further examples of the alkyl group include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t-Bu, -C(CH3)3), n-pentyl (-CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH (CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), n-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl     (-CH(CH3)CH(CH3)CH2CH3),     4-methyl-2-pentyl     (- CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3), n-heptyl, n-octyl, etc. As used herein, the term “alkyl” and its prefix “alk-”, encompass both linear and branched saturated carbon chains. The term "alkylene" refers to a saturated divalent hydrocarbon group obtained by the removal of two hydrogen atoms from a saturated linear or branched hydrocarbon group. Unless otherwise specified, the alkylene group contains 1-12 carbon atoms. In some embodiments, the alkylene group contains 1-6 carbon atoms; in other embodiments, the alkylene group contains 1-4 carbon atoms; in still other embodiments, the alkylene group contains 1-3 carbon atoms; in yet other embodiments, the alkylene group contains 1-2 carbon atoms. Examples thereof include methylene (-CH2-), ethylene (-CH2CH2-), isopropylene (-CH(CH3)CH2-), etc. The term “alkenyl” refers to a linear or branched monovalent hydrocarbon group having 2-12 carbon atoms, or 2-8 carbon atoms, or 2-6 carbon atoms, or 2-4 carbon atoms, wherein at least one position is unsaturated, i.e., one C-C is an sp2 double bond, and the alkenyl group may be independently and optionally substituted with one or more substituents described in the present invention, including groups having "trans", "cis" or "E", "Z" configurations. Specific examples of alkenyl include, but are not limited to, vinyl (-CH=CH2), allyl (-CH2CH=CH2), etc. The term “alkynyl” refers to a linear or branched monovalent hydrocarbon group having 2-12 carbon atoms, or 2-8 carbon atoms, or 2-6 carbon atoms, or 2-4 carbon atoms, wherein at least one position is unsaturated, i.e., one C-C is an sp triple bond, and the alkynyl group may be independently and optionally substituted with one or more substituents described in the present invention. Specific examples of alkynyl include, but are not limited to, ethynyl (-C=CH), propargyl (-CH2C=CH), etc. The term "heteroatom" refers to one or more of O, S, N, P, and Si, including any oxidised form of C, N, S, and P; the forms of primary, secondary, tertiary amines, and quaternary ammonium salts; or the forms in which the hydrogen on a nitrogen atom in a heterocycle is substituted, e.g., N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidyl) or NR (as in N-substituted pyrrolidyl); or the forms in which -CH2- in a heterocycle is oxidised to form -C(=O)-. The term “halogen” refers to F, Cl, Br or I. The term "deuterium" refers to heavy hydrogen, D. The term “unsaturated” as used in the present invention means that the moiety contains one or more degrees of unsaturation. The term “alkoxy” or “alkyloxy” as used in the present invention refers to an alkyl group, as defined in the present invention, attached to the remainder of the compound molecule via an oxygen atom. In some embodiments, the alkoxy is C1-4 alkoxy; and examples thereof include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, etc. The alkoxy may be independently unsubstituted or substituted with one or more substituents described in the present invention. The term “alkylthio” or “alkylsulphanyl” as used in the present invention refers to an alkyl group, as defined in the present invention, attached to the remainder of the compound molecule via a sulphur atom. In some embodiments, the alkylthio is C1-4 alkylthio; and examples thereof include, but are not limited to, methylthio, ethylthio, propylthio, butylthio, etc. The alkylthio may be independently unsubstituted or substituted with one or more substituents described in the present invention. The term “alkylamino” as used in the present invention refers to an alkyl group, as defined in the present invention, attached to the remainder of the compound molecule via a N atom. In some embodiments, the alkylamino is C1-4 alkylamino; examples thereof include, but are not limited to, methylamino, ethylamino, propylamino, butylamino, etc. The alkylamino may be independently unsubstituted or substituted with one or more substituents described in the present invention. The term "cycloalkyl" or "cycloalkane" refers to a monovalent or multivalent monocyclic, bicyclic, or tricyclic carbocyclic ring system containing 3-12 carbon atoms, which is saturated or contains one or more unsaturated bonds, but is by no means aromatic. The “cycloalkyl” or “cycloalkane” may also be a bridged ring and a spiro ring. In one embodiment, the cycloalkyl contains 3-10 carbon atoms; in another embodiment, the cycloalkyl contains 3-8 carbon atoms; in still another embodiment, the cycloalkyl contains 3-6 carbon atoms. Examples thereof include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, etc. The cycloalkyl group may be independently unsubstituted or substituted with one or more substituents described in the present invention. The terms “heterocyclyl” and “heterocycle” are used interchangeably herein, and both refer to a saturated or partially unsaturated monocyclic, bicyclic, or tricyclic ring containing 3-12 ring atoms, which is by no means aromatic, wherein at least one of the ring atoms is a heteroatom. The “heterocyclyl” or “heterocycle” may also be a bridged heterocycle and a spiro heterocycle. In one embodiment, the “heterocyclyl” or “heterocycle” contains 3-10 ring atoms; in one embodiment, the “heterocyclyl” or “heterocycle” contains 3-8 ring atoms; in another embodiment, the “heterocyclyl” or “heterocycle” contains 5-8 ring atoms; in still another embodiment, the “heterocyclyl” or “heterocycle” contains 3-6 ring atoms; in yet another embodiment, the “heterocyclyl” or “heterocycle” contains 5-6 ring atoms; in a further embodiment, the “heterocyclyl” or “heterocycle” contains 4-6 ring atoms. Unless otherwise specified, the heterocyclyl may be carbon-attached or nitrogen-attached, and the heteroatom has the meaning as described in the present invention. Examples of heterocyclyl include, but are not limited to: oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuryl, dihydrofuryl, tetrahydrothienyl, dihydrothienyl, 1,3-dioxolanyl, dithiolanyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thioxanyl, homopiperazinyl, homopiperidyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 2-oxa-5-azabicyclo[2.2.1]hept-5-yl, 2-oxabicyclo[2.1.1]hexane and 1,2,3,6-tetrahydropyridyl. Examples of heterocyclyl in which a -CH2- group is substituted with -C(=O)- include, but are not limited to: 2-oxopyrrolidyl, oxo-1,3-thiazolidinyl, 2-piperidinonyl, 3,5-dioxopiperidyl, pyrimidinedionyl and 5,6-dihydropyridin-2(1H)-onyl. Examples of heterocyclyl in which a sulphur atom is oxidised include, but are not limited to, sulpholanyl and 1,1-dioxothiomorpholinyl. The heterocyclyl group may be optionally substituted with one or more substituents described in the present invention. The term “aryl” refers to a monocyclic, bicyclic, or tricyclic carbocyclic ring system containing 6-14 ring atoms, or 6-12 ring atoms, or 6-10 ring atoms, wherein at least one ring is aromatic, and each ring contains 3-7 ring atoms. The ring system has one or more points of attachment to the remainder of the molecule. The term "aryl" may be used interchangeably with the term "aromatic ring". Examples of the aryl group may include phenyl, naphthyl, and anthracenyl. The aryl group may be independently and optionally substituted with one or more substituents described in the present invention. The term “heteroaryl” refers to a monocyclic, bicyclic, or tricyclic ring system containing 5-12 ring atoms, or 5-10 ring atoms, or 5-6 ring atoms, wherein at least one ring system is aromatic, at least one ring system contains one or more heteroatoms, and each ring contains 5-7 ring atoms. The ring system has one or more points of attachment to the remainder of the molecule. The term "heteroaryl" may be used interchangeably with the term "heteroaromatic ring” or “heteroaromatic compound”. The heteroaryl group is optionally substituted with one or more substituents described in the present invention. In one embodiment, the heteroaryl consisting of 5-10 atoms comprises 1, 2, 3 or 4 heteroatoms independently selected from O, S and N, wherein the nitrogen atom may be further oxidised. Examples of the heteroaryl group include, but are not limited to: furyl, imidazolyl (such as N-imidazolyl, 2-imidazolyl, 4-imidazolyl, and 5-imidazolyl), isoxazolyl, oxazolyl (such as 2-oxazolyl, 4-oxazolyl, and 5-oxazolyl), pyrrolyl (such as N-pyrrolyl, 2-pyrrolyl, and 3-pyrrolyl), pyridyl, pyrimidyl (such as 2-pyrimidyl, 4-pyrimidyl, and 5-pyrimidyl), pyridazinyl, thiazolyl (such as 2-thiazolyl, 4-thiazolyl, and 5-thiazolyl), tetrazolyl (such as 5-tetrazolyl), triazolyl, thienyl (such as 2-thienyl and 3-thienyl), pyrazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, pyrazinyl, and 1,3,5-triazinyl; and also the following bicyclic groups, but by no means limited to these bicyclic groups: benzimidazolyl, benzofuryl, benzothienyl, indolyl (such as 2-indolyl), purinyl, quinolyl (such as 2-quinolyl, 3-quinolyl, and 4-quinolyl), 1,2,3,4-tetrahydroisoquinolyl, 1,3-benzodioxolyl, indolinyl, isoquinolyl (such as 1-isoquinolyl, 3-isoquinolyl or 4-isoquinolyl), imidazo[1,2-a]pyridyl,  pyrazolo[1,5-a]  pyridyl, pyrazolo[1,5- a]pyrimidyl,     imidazo[1,2-b]pyridazinyl,     [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidyl, [1,2,4]triazolo[1,5-a]pyridyl, etc. The term "haloalkyl" or "haloalkoxy" refers to an alkyl or alkoxy group substituted with one or more halogen atoms. Examples thereof include, but are not limited to, trifluoromethyl, trifluoromethoxy, etc. The term "halocycloalkyl" refers to a cycloalkyl group substituted with one or more halogen atoms. Examples thereof include, but are not limited to, 1,1-difluorocyclopropane, 1-chloro-2-fluorocyclopropane, etc. As described in the present invention, a substituent drawn with a bond connected to a ring of a ring system indicates that the substituent may be substituted at any substitutable position on that ring. For example, formula (a) indicates that the pyridine ring may be monosubstituted or polysubstituted with the substituent R at any substitutable position thereof. (R)p N (a) As described in the present invention, a wavy line that intersects a bond in a chemical structure denotes the point where the atom connected to the wavy bond is attached to the remainder of the molecule or a fragment of the molecule. Furthermore, it should be noted that, unless otherwise explicitly stated, the descriptions “each ... and ... are independently”, “... and ... are each independently”, and “... and ... are independently” as used throughout the text are interchangeable and should be understood in a broad sense. The descriptions not only mean that the specific options represented by identical symbols in different groups do not affect each other, but also mean that the specific options represented by identical symbols in the same groups do not affect each other. Unless otherwise indicated, the structural formulas described in the present invention include all isomeric forms (e.g., enantiomers, diastereomers, geometric isomers or conformational isomers), such as R and S configurations containing asymmetric centres, (Z) and (E) isomers for double bonds, and (Z) and (E) conformational isomers. Accordingly, individual stereochemical isomers and mixtures of enantiomers, diastereomers, geometric isomers or conformational isomers of the compounds of the present invention fall within the scope of the present invention. Unless otherwise indicated, the structural formulas and the compounds described in the present invention include all isomeric forms (e.g., enantiomers, diastereomers, geometric isomers or conformational isomers), nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts and prodrugs. Accordingly, individual stereochemical isomers, enantiomers, diastereomers, geometric isomers, conformational isomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts and prodrugs of the compounds of the present invention also fall within the scope of the present invention. In addition, unless otherwise indicated, the structural formulas of the compounds described in the present invention include compounds in which one or more different atoms are present in an isotopically enriched form. “Metabolite” refers to a product obtained by metabolism in the body from a specific compound described in the present invention, or a pharmaceutically acceptable salt, analogue, or derivative thereof, which product exhibits activity in vivo or in vitro similar to that of a compound of formula (I). The metabolite of a compound may be identified by techniques known in the art, and its activity may be characterised by experimental methods as described in the present invention. Such products may be obtained, for example, by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, delipidation, enzymatic cleavage, etc, of an administered compound. Accordingly, the present invention encompasses metabolites of the compounds, including metabolites produced by contacting a compound of the present invention with a mammal for a sufficient period of time. The definitions and conventions of stereochemistry used in the present invention generally refer to the following literature: S. P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley&Sons, Inc., New York, 1994. The compounds of the present invention may comprise asymmetric centres or chiral centres, and therefore exist as different stereoisomers. All stereoisomeric forms of the compounds of the present invention, including, but by no means limited to, diastereomers, enantiomers, atropisomers, and mixtures thereof, such as racemic mixtures, form part of the present invention. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarised light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of a molecule with respect to its chiral centres. The prefixes d and l or (+) and (-) are the symbols used to designate the rotation of plane-polarised light cause by a compound, where (-) or l indicates that the compound is levorotatory, and (+) or d indicates that the compound is dextrorotatory. These stereoisomers are identical in chemical structure but differ in their stereostructure. A specific type of stereoisomer may be an enantiomer, and a mixture of such isomers is often referred to as an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture or racemate, which may result in no stereoselectivity or stereospecificity in a chemical reaction. The terms “racemic mixture” and “racemate” refers to an equimolar mixture of two enantiomers, which is not optically active. The term "tautomer" or "tautomeric form" refers to structural isomers of different energies which are interconvertible via a low-energy barrier. For example, proton tautomers (i.e., prototropic tautomers) include interconversions via migration of a proton, such as keto-enol and imine-enamine isomerisations. Valence tautomers include interconversions by reorganisation of bonding electrons. "Pharmaceutically acceptable salt" as used in the present invention refers to organic salts and inorganic salts of the compounds of the present invention. Pharmaceutically acceptable salts are well known in the art, for example, as described in the literature: S. M. Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66: 1-19, 1977. Pharmaceutically acceptable salts formed with non-toxic acids include, but are not limited to: inorganic acid salts formed by reaction with amino groups, such as hydrochloride, hydrobromide, phosphate, sulphate, and perchlorate; organic acid salts, such as acetate, oxalate, maleate, tartrate, citrate, succinate, and malonate; or salts obtained by using other methods described in the literature such as ion exchange. Other pharmaceutically acceptable salts include adipate, malate, 2-hydroxypropionate, alginate, ascorbate, aspartate, benzenesulphonate, benzoate, bisulphate, borate, butyrate, camphorate, camphorsulphonate, cyclopentanepropionate, digluconate, dodecylsulphate, ethanesulphonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulphate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulphonate, lactobionate, lactate, laurate, laurylsulphate, malate, methanesulphonate, 2-naphthalenesulphonate, nicotinate, nitrate, oleate, palmitate, pamoate, pectinate, persulphate, 3-phenylpropionate, picrate, pivalate, propionate, stearate, thiocyanate, p-toluenesulphonate, undecanoate, valerate, etc. Salts obtained using appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts and N+(C1-4 alkyl)4 salts. The present invention also contemplates quaternary ammonium salts formed from any compound containing an N-containing group. Water-soluble or oil-soluble or dispersible products may be obtained by quaternisation. Alkali metals or alkaline earth metals that can form salts include sodium, lithium, potassium, calcium, magnesium, etc. Pharmaceutically acceptable salts further include appropriate and non-toxic ammonium, quaternary ammonium salts, and amine cations formed with counterions, such as halide, hydroxide, carboxylate, sulphate, phosphate, nitrate, C1-8 sulphonate, and aromatic sulphonate. “Hydrate” as used in the present invention refers to an association in which the solvent molecules are water. “Solvate” as used in the present invention refers to an association formed by one or more solvent molecules with the compound of the present invention. Solvents that form solvates include, but are not limited to: water, isopropanol, ethanol, methanol, dimethyl sulphoxide, ethyl acetate, acetic acid and ethanolamine. “Ester” as used in the present invention refers to an in vivo hydrolysable ester of a compound of formula (I) that contains hydroxyl. Such esters are, for example, pharmaceutically acceptable esters that undergo hydrolysis in the human or animal body to yield the parent alcohol. Groups for in vivo hydrolysable esters of a compound of formula (I) that contains hydroxyl include, but are not limited to: phosphate group, acetoxymethoxy, 2,2-dimethylpropionyloxymethoxy, alkanoyl, benzoyl,        phenylacetyl,        alkoxycarbonyl,        dialkylcarbamoyl, N-(dialkylaminoethyl)-N-alkylcarbamoyl, etc. “Nitrogen oxide” as used in the present invention refers to an N-oxide formed by oxidising one or more nitrogen atoms when a compound contains several amine functional groups. Special examples of N-oxides are N-oxides of tertiary amines or N-oxides of nitrogen atoms on nitrogen-containing heterocycles. The N-oxide can be formed by treating corresponding amines with oxidising agents such as hydrogen peroxide or peracids (e.g., peroxycarboxylic acids) (see Advanced Organic Chemistry, Wiley Interscience, 4th Edition, Jerry March, pages). Especially, the N-oxide can be prepared by the method of L.W.Deady (Syn.Comm.1977, 7, 509-514), for example, by reacting an amine compound with m-chloroperoxybenzoic acid (MCPBA) in an inert solvent such as dichloromethane. The term “prodrug” as used in the present invention refers to a compound that is converted in vivo into a compound as shown in formula (I). Such conversion is effected by hydrolysis of the prodrug in the blood or enzymatic conversion of the prodrug to the parent structure in the blood or tissues. The prodrug compounds of the present invention may be esters, and esters that may serve as prodrugs in the prior art include phenyl esters, aliphatic (C1-24) esters, acyloxymethyl esters, carbonates, carbamates, and amino acid esters. For example, when a compound of the present invention comprises hydroxyl, it can be acylated to obtain a compound in prodrug form. Other prodrug forms include phosphate esters, such as those obtained by phosphorylation of hydroxyl on the parent compound. For a complete discussion of prodrugs, reference may be made to the following literature: T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, J. Rautio et al, Prodrugs: Design and Clinical Applications, Nature Review Drug Discovery, 2008, 7, 255-270, and S. J. Hecker et al, Prodrugs of Phosphates and Phosphonates, Journal of Medicinal Chemistry, 2008, 51, 2328-2345. Unless otherwise specified herein or the context clearly dictates otherwise, the terms “a”, “an”, “the” and similar terms used in the context of the present invention (especially in the context of the claims) can be construed to cover both the singular and plural forms. General synthesis process The following examples are provided to illustrate the present invention. However, it should be understood that the present invention is not limited to these examples, which merely provide a method for practicing the present invention. Generally, the compounds of the present invention may be prepared by the methods described in the present invention, wherein the substituents are as defined in the present invention unless otherwise indicated. The following reaction schemes and examples are provided to further illustrate the content of the present invention. Those skilled in the art will recognise that the chemical reactions described in the present invention may be suitably used to prepare other compounds of the present invention, and other methods for preparing the compounds of the present invention are considered to be within the scope of the present invention. For example, the non-exemplified compounds of the present invention can be successfully synthesised by those skilled in the art by making modifications, such as appropriately protecting interfering groups, using other known reagents besides those described in the present invention, or making routine variations to the reaction conditions. In addition, the reactions disclosed in the present invention or known reaction conditions are also generally accepted to be applicable to the preparation of other compounds of the present invention. Unless otherwise specified, the starting materials, reagents, etc. used in the following examples are all commercially available or obtained via synthetic routes known from the literature. The equipment and detection conditions are described as follows: 1H NMR spectra were recorded on a Bruker 500 MHz nuclear magnetic resonance spectrometer. 1H NMR spectra were obtained using CDCl3, DMSO-d6, CD3OD or acetone-d6 as solvents (in ppm), with TMS (0 ppm) or chloroform (7.26 ppm) as the reference standard. When multiple peaks appear, the following abbreviations will be used: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broadened), brs (broadened singlet), dd (doublet of doublets), and dt (doublet of triplets). The coupling constant J is expressed in Hertz (Hz). Low-resolution mass spectrometry (MS) data were measured under the following conditions: Agilent G6125C quadrupole HPLC-MS (chromatographic column model: XBridge BEH C18, 4.6 x 50 mm, 2.5 microns, 6 min, flow rate 1 mL / min; mobile phase: 0% - 95% (CH3CN) in (H2O : CH3CN = 90 : 10 containing 0.1% formic acid), using electrospray ionisation (ESI), with DAD detection at 210 nm / 254 nm. Compounds were named according to conventional nomenclature principles in the art or by using software, and commercially available compounds are designated by the names provided in the supplier's catalogue. Detailed Description of Embodiments The present invention will be described below with reference to specific embodiments. It should be noted that these embodiments are only illustrative and do not limit the present invention in any way. Example 1 1-1 COOH 1-11 F F 1-13 Example 1 Preparation of compound 1-2 Under a nitrogen atmosphere, compound 1-1 (40 g, 253 mmol) was dissolved in THF (200 mL), and a solution of methyllithium lithium bromide in diethyl ether 5   (506 mL, 759 mmol) was slowly added dropwise at 0°C. After the dropwise addition was completed, the mixture was slowly warmed to room temperature, and stirred for 16 hours. After the reaction was completed, the reaction solution was cooled to 0°C. The reaction was quenched by dropwise addition of water (200 mL). The mixture was stirred for 1 hour, and then extracted with dichloromethane (200 mL x 5). The 10 combined organic phases were dried over anhydrous sodium sulphate, filtered, and distilled at 60°C-100°C until no more distillate came over. The residue remaining in the flask was a solution of compound 1-2 in THF. 1H NMR (400 MHz, CDCI3): d 2.36 (s, 3H), 1.52 (s, 3H). Preparation of compound 1-3 15       The preparation route of compound 1-3 was as follows: OH ho-b' 1-4                                             1-6                                  1-3 Compound 1-4 (33.2 mL, 299.40 mmol), compound 1-5 (61.90 g, 329.34 mmol), potassium carbonate (140.68 g, 1017.96 mmol), and cuprous oxide (1.30 g, 8.98 mmol) were sequentially added to toluene (1000 mL). Under a nitrogen atmosphere, tetrakis(triphenylphosphine)palladium (10.38 g, 8.98 mmol) was added, and the mixture was stirred at 25°C for 16 hours. The reaction solution was concentrated, and water (500 mL) was added. The mixture was extracted with ethyl acetate (500 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 8 : 1) to obtain compound 1-6. Compound 1-6 (29 g, 126 mmol) was dissolved in THF (250 mL), and aqueous lithium hydroxide solution (144.9 mL, 289.74 mmol, 2 mole / liter) was added. The reaction solution was warmed to 50°C and stirred for 1 hour. After the reaction was completed, the mixture was cooled to room temperature, and washed with dichloromethane (200 mL x 1). The aqueous phase was adjusted to pH=1 with dilute hydrochloric acid (1 mole / liter). The mixture was extracted with dichloromethane (100 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain compound 1-3. Preparation of compound 1-7 Under a nitrogen atmosphere, compound 1-3 (7.72 g, 38.2 mmol) was dissolved in acetonitrile (80 mL), and carbonyldiimidazole (6.50 g, 40.08 mmol) was added at 0°C. The mixture was stirred for 1 hour, and then potassium carbonate (6.59 g, 47.7 mmol) and compound 1-2 (26.6 g, 38.2 mmol, 22.4% content) were sequentially added. The reaction solution was warmed to 35°C and stirred for 10 hours. After the reaction was completed, the mixture was subjected to suction filtration to remove solids, and the filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 10 : 1) to obtain compound 1-7. 1H NMR (400 MHz, CDCI3): 3 7.00 - 6.87 (m, 2H), 3.92 (d, J = 2.1 Hz, 3H), 2.05 (s, 3H), 1.76 (s, 3H). Preparation of compound 1-8 Under a nitrogen atmosphere, palladium on carbon (3 g, 10% content) was added to 17.5 mL of isopropanol, and compound 1-7 (3 g, 9.31 mmol) was added with stirring at room temperature. The reaction solution was stirred at 30°C under a hydrogen atmosphere (225 psi) for 30 hours. The reaction solution was filtered through Celite, and the filter cake was washed sequentially with 100 mL of isopropanol and 20 mL of dichloromethane. The filtrate was concentrated under reduced pressure, and then the residue was co-evaporated with 50 mL of toluene twice to obtain compound 1-8. 1H NMR (400 MHz, CDCI3): 5 7.00 - 6.93 (m, 1H), 6.92 - 6.84 (m, 1H), 4.49 (d, J = 9.0 Hz, 1H), 4.04 (d, J = 2.9 Hz, 3H), 2.96 - 2.83 (m, 1H), 1.72 (s, 3H), 0.81 (dd, J = 2.1, 4.9 Hz, 3H); m / z (ESI): [M + H]+=325.1. Preparation of compound 1-9 Under a nitrogen atmosphere, diisobutylaluminium hydride (13.0 mL, 13.0 mmol, 1 mole / liter in toluene) was slowly added dropwise to a solution of compound 1-8 (2.8 g, 8.64 mmol) in toluene (30 mL) at -30°C. After the dropwise addition was completed, the reaction solution was stirred at -30°C for another 1.5 hours. After the reaction was completed, the mixture was diluted with 100 mL of ethyl acetate and warmed to 0°C. The reaction was quenched by dropwise addition of saturated aqueous ammonium chloride solution, and stirred for 0.5 hours. The mixture was filtered through Celite, and then subjected to liquid separation. The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain compound 1-9. 1H NMR (400 MHz, CDCl3): 3 6.95 - 6.89 (m, 1H), 6.89 - 6.80 (m, 1H), 5.80 (t, J = 3.5 Hz, 1H), 4.00 (d, J = 2.6 Hz, 3H), 3.88 - 3.78 (m, 1H), 2.99 - 2.84 (m, 2H), 1.65 (s, 3H), 0.90 - 0.77 (m, 3H). Preparation of compound 1-10 Compound 1-9 (2.4 g, 7.36 mmol), 4-dimethylaminopyridine (1.35 g, 11.03 mmol) and acetic anhydride (1.0 mL, 11.0 mmol) were sequentially added to 40 mL of dichloromethane with stirring at room temperature. The reaction solution was stirred at 20°C for 1 hour. After the reaction was completed, the reaction solution was slowly poured into 30% aqueous ammonium chloride solution (100 mL) to quench the reaction. The organic phase was washed with 10% aqueous sodium carbonate solution (100 mL), dried over anhydrous sodium sulphate, and then concentrated under reduced pressure to obtain compound 1-10. 1H NMR (400 MHz, CDCI3): S 7.00 - 6.91 (m, 1H), 6.91 - 6.81 (m, 1H), 6.56 (d, J = 2.3 Hz, 1H), 4.01 - 3.99 (m, 3H), 3.96 (dd, J = 2.0, 8.9 Hz, 1H), 2.96 - 2.86 (m, 1H), 2.11 (s, 3H), 1.62 (s, 3H), 0.87 (dd, J = 1.9, 7.6 Hz, 3H). Preparation of compound 1-11 Under a nitrogen atmosphere, compound 1-10 (2.6 g, 7.06 mmol) was added to 40 mL of dichloromethane. The mixture was cooled to -30°C, and then trimethylsilyl cyanide (2.8 mL, 21.2 mmol) was slowly added to the reaction solution. The mixture was stirred for 5 minutes, and then boron trifluoride diethyl ether (7.8 mL, 28.2 mmol) was added dropwise. The reaction solution was stirred at -30°C-0°C for 2 hours. After the reaction was completed, aqueous potassium hydroxide solution (2 mol / L, 100 mL) was slowly added dropwise. The mixture was extracted with dichloromethane (50 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain compound 1-11. 1H NMR (400 MHz, CDCl3): S 6.93 - 6.85 (m, 1H), 6.78 - 6.76 (m, 1H), 5.08 -5.01 (m, 1H), 4.26 - 4.21 (m, 1H), 4.08 - 4.05 (m, 3H), 2.89 -2.81 (m, 1H), 1.64 (s, 3H),0.83 - 0.79 (m, 3H). Preparation of compound 1-12 Compound 1-11 (2.4 g, 7.16 mmol) was added to 20 mL of ethanol, and aqueous potassium hydroxide solution (20 mL, 2 mol / L) was added dropwise with stirring. The reaction solution was warmed to 75°C and stirred for 16 hours. After the reaction was completed, the mixture was cooled, diluted with 100 mL of water, and then concentrated under reduced pressure to remove ethanol. 50 mL of ethyl acetate was added to the concentrate, and the mixture was subjected to liquid separation. The aqueous phase was adjusted to pH = 5 with 6 M hydrochloric acid and extracted with ethyl acetate (50 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by reversed-phase column chromatography (mobile phase A: water (0.1% formic acid), B: acetonitrile; elution gradient: B: 70%-80% over 15 minutes) to obtain compound 1-12. 1H NMR(400 MHz, DMSO-d6) 8 13.13 - 12.80 (m, 1H), 7.22 - 7.16 (m, 1H), 7.16 - 7.09 (m, 1H), 4.98 (d, J = 10.4 Hz, 1H), 4.08 (dd, J = 7.9, 10.8 Hz, 1H), 3.93 (d, J = 2.1 Hz, 3H), 2.73 - 2.60 (m, 1H), 1.53 (s, 3H), 0.74 - 0.64 (m, 3H). m / z (ESI): [M-H]- = 353.2. Preparation of compound 1-13 Compound 1-12 (2.1 g, 5.93 mmol) was added to 4 mL of toluene. The mixture was warmed to 60°C with stirring, and a solution of (R)-l-phenylethylamine (0.86 g, 7.11 mmol) in toluene (4 mL) was slowly added dropwise. After the dropwise addition was completed, the reaction was cooled to 50°C. The mixture was stirred for 1 hour, slowly cooled to 20°C, and then stirred at 20°C for 8 hours. The resulting mixture was filtered. The filter cake was washed with 5 mL of toluene and dried to obtain compound 1-13. 1H NMR (400 MHz, MeOD): 8 7.50 - 7.41 (m, 5H), 7.13 (ddd, J = 2.1, 6.0, 8.6 Hz, 1H), 6.96 - 6.87 (m, 1H), 4.73 (d, J = 10.4 Hz, 1H), 4.48 - 4.38 (m, 1H), 4.09 (dd, J = 8.3, 10.1 Hz, 1H), 3.96 (d, J = 2.1 Hz, 3H), 2.58 - 2.48 (m, 1H), 1.65 - 1.57 (m, 6H), 0.78 - 0.70 (m, 3H). Preparation of compound 1-14 Compound 1-13 (2.25 g, 4.73 mmol) was added to a mixed solution of 20 mL of isopropanol and 40 mL of n-heptane. 40 mL of dichloromethane and 40 mL of aqueous hydrochloric acid solution (2 -mol / L) were sequentially added with stirring. The reaction solution was stirred for half an hour and then concentrated under reduced pressure to remove the low-boiling solvents. 50 mL of ethyl acetate was added to the residue, and the mixture was extracted and subjected to liquid separation. The organic phase was washed with 20 mL of water, dried over anhydrous sodium sulphate, and concentrated under reduced pressure to obtain an oil (1.76 g). Quinine (1.56 g, 4.80 mmol) was added to a solution of the above oil in dichloromethane (4 mL). 4 mL of isopropanol was added, and the mixture was warmed to 70°C (to distil off the low-boiling dichloromethane). The reaction solution was cooled to 65°C, and 12 mL of n-heptane was slowly added. The mixture was stirred at 65°C for 1 hour. Then the reaction solution was slowly cooled to 20°C and stirred at 20°C for 2 hours. The mixture was filtered, and the filter cake was washed with isopropanol / n-heptane = 1 / 3 (3 mL) and dried under reduced pressure to obtain compound 1-14. 1H NMR (400 MHz,CDCl3) 8 8.68 (d, J = 4.5 Hz, 1H), 7.84 (d, J = 9.1 Hz, 1H), 7.60 (d, J = 4.4 Hz, 1H), 7.18 (dd, J = 2.6, 9.3 Hz, 1H), 7.10 (ddd, J = 1.8, 6.1, 8.4 Hz, 1H), 6.84 - 6.75 (m, 2H), 6.16 (s, 1H), 5.52 (ddd, J = 6.7, 10.4, 17.2 Hz, 1H), 5.06 - 4.92 (m, 2H), 4.85 (d, J = 10.1 Hz, 1H), 4.37 - 4.23 (m, 1H), 4.17 - 4.07 (m, 1H), 3.93 (d, J = 2.5 Hz, 3H), 3.70 (s, 3H), 3.39 - 3.24 (m, 2H), 3.07 - 2.91 (m, 2H), 2.60 - 2.48 (m, 1H), 2.58 (d, J = 1.5 Hz, 1H), 2.15 - 2.04 (m, 1H), 2.03 - 1.93 (m, 2H), 1.80 - 1.68 (m, 1H), 1.65 (s, 3H), 1.27 - 1.10 (m, 1H), 0.78 (dd, J = 1.8, 7.3 Hz, 3H). Preparation of compound 1-15 20 mL of dilute hydrochloric acid (2.5 mol / L) was added dropwise to a solution of compound 1-14 (1.6 g, 2.36 mmol) in 20 mL of dichloromethane. The mixture was stirred at 20°C for half an hour and then allowed to stand for liquid separation. 30 mL of dilute hydrochloric acid (2.5 mol / L) was added again to the organic phase, and the mixture was subjected to liquid separation. The combined aqueous phases were extracted with dichloromethane (20 mL x 2). The combined organic phases were washed with 20 mL of water, dried over anhydrous sodium sulphate, and concentrated to obtain a white solid (600 mg). Under a nitrogen atmosphere, DMF (0.1 mL, 0.34 mmol) and oxalyl chloride (0.3 mL, 3.39 mmol) were sequentially added dropwise to a solution of the above white solid (600 mg, 1.69 mmol) in 10 mL of dichloromethane at 0°C. The reaction solution was warmed to room temperature, stirred for 2 hours, and concentrated under reduced pressure to obtain compound 1-15. Preparation of compound 1-16 Under a nitrogen atmosphere, compound 1-15 (200 mg, 0.54 mmol) was slowly added to a solution of methyl 4-amino-2-pyridinecarboxylate (163.3 mg, 1.07 mmol) and triethylamine (0.2 mL, 1.61 mmol) in 4 mL of dichloromethane at 0°C. The mixed solution was warmed to 20°C and stirred for 2 hours. After the reaction was completed, the reaction solution was quenched by dropwise addition of 20 mL of water and extracted with dichloromethane (10 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated to obtain a crude product. The crude product was purified by reversed-phase column chromatography (mobile phase A: water (0.1% aqueous ammonia), B: acetonitrile; elution gradient: B: 70%-80% over 15 minutes) to obtain compound 1-16. 1H NMR (400 MHz, CDCI3): 8 8.64 (d, J = 5.4 Hz, 1H), 8.58 (s, 1H), 8.09 (d, J = 2.1 Hz, 1H), 7.94 (dd, J = 2.3, 5.5 Hz, 1H), 7.12 - 7.05 (m, 1H), 6.97 - 6.88 (m, 1H), 5.04 (d, J = 11.1 Hz, 1H), 4.21 - 4.06 (m, 2H), 2.84 - 2.70 (m, 1H), 1.70 (s, 3H), 1.56 (s, 4H), 0.86 - 0.75 (m, 3H); m / z (ESI): [M+ H]+ = 489.2. Preparation of compound 1-17 Compound 1-16 (210 mg, 0.43 mmol) was added to a 7 mol / L ammonia / methanol solution (6.1 mL, 43.00 mmol). The reaction solution was reacted at 40°C for 24 hours in a PTFE sealed vessel. After the reaction was completed, the mixture was concentrated to obtain a crude product. The crude product was separated and purified by preparative high-performance liquid chromatography (column model: Phenomenex luna C18 150*25 mm*10 um; mobile phase: [A: water (0.1% formic acid), B: acetonitrile; elution gradient: B%: 40%-70% over 10 minutes) to obtain compound 1-17. 1H NMR (400 MHz, DMSO-d6): 8 10.74 (s, 1H), 8.49 (d, J = 5.5 Hz, 1H), 8.28 (d, J = 2.0 Hz, 1H), 8.07 (br d, J = 2.1 Hz, 1H), 7.83 (dd, J = 2.1, 5.5 Hz, 1H), 7.63 (s, 1H), 7.22 - 7.12 (m, 2H), 5.10 (d, J = 10.3 Hz, 1H), 4.25 (dd, J = 7.9, 10.1 Hz, 1H), 3.94 (d, J = 2.0 Hz, 3H), 2.83 - 2.71 (m, 1H), 1.61 (s, 3H), 0.73 (d, J = 6.5 Hz, 3H); m / z (ESI): [M+ H]+ = 474.4. Preparation of compound 1-18 Under a nitrogen atmosphere, boron tribromide (0.30 mL, 0.32 mmol) was slowly added dropwise to a solution of compound 1-17 (100 mg, 0.21 mmol) in 2 mL of dichloromethane at 0°C. After the dropwise addition was completed, the mixture was stirred at 0°C for 2 hours. After the reaction was completed, the reaction solution was poured into 50 mL of saturated aqueous sodium bicarbonate solution to quench the reaction. The aqueous phase was extracted with ethyl acetate (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified by preparative silica gel thin-layer chromatography (dichloromethane / methanol = 10 : 1) to obtain compound 1-18. 1H NMR (400 MHz, DMSO-d6): S 10.74 (s, 1H), 10.53 - 10.41 (m, 1H), 8.49 (d, J = 5.5 Hz, 1H), 8.27 (s, 1H), 8.06 (s, 1H), 7.83 (dd, J = 2.1, 5.5 Hz, 1H), 7.62 (br s, 1H), 7.03 (t, J = 7.1 Hz, 1H), 6.86 (q, J = 8.9 Hz, 1H), 5.10 (d, J = 10.3 Hz, 1H), 4.30 - 4.20 (m, 1H), 2.90 - 2.78 (m 1H), 2.54 (d, J = 1.0 Hz, 2H), 1.60 (s, 3H), 0.71 (d, J = 6.3 Hz, 3H); m / z (ESI): [M+ H]+ = 460.2. Preparation of example 1 Under a nitrogen atmosphere, bromopropyne (2.38 mg, 0.02 mmol) was slowly added dropwise to a solution of compound 1-18 (10 mg, 0.02 mmol) and potassium carbonate (13.8 mg, 0.02 mmol) in DMF (1 mL). After the dropwise addition was completed, the mixture was warmed to 60°C and reacted for 2 hours. The reaction solution was cooled and filtered, and the filtrate was separated and purified by preparative high-performance liquid chromatography (column model: Waters Xbridge 150*25 mm*5 gm; mobile phase A: water (aqueous ammonia), B: acetonitrile; elution gradient: B%: 42%-72% over 11 minutes) to obtain example 1. 1H NMR (400 MHz, CDCl3): S 8.68 (s, 1H), 8.46 (d, J = 5.6 Hz, 1H), 8.16 (dd, J = 2.2, 5.6 Hz, 1H), 7.94 (d, J = 2.1 Hz, 1H), 7.84 (s, 1H), 7.19 - 7.11 (m, 1H), 7.05 - 6.94 (m, 1H), 5.67 - 5.56 (m, 1H), 5.02 (d, J = 11.4 Hz, 1H), 4.93 - 4.74 (m, 2H), 4.26 (dd, J = 7.8, 11.3 Hz, 1H), 2.90 - 2.79 (m, 1H), 2.38 (t, J = 2.4 Hz, 1H), 1.72 (s, 3H), 0.86 - 0.77 (m, 3H); m / z (ESI): [M+ H]+ = 498.2. Example 2 F F                                                   F F ^18                                    Example 2 Under a nitrogen atmosphere, 1-bromo-2-butyne (14.5 mg, 0.11 mmol) was slowly added dropwise to a solution of compound 1-18 (50 mg, 0.11 mmol) and potassium carbonate (75.2 mg, 0.54 mmol) in 1 mL of DMF. The reaction solution was warmed to 60°C and reacted for 2 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was separated and purified by preparative high-performance liquid chromatography (column model: Waters Xbridge 150*25 mm*5 pm; mobile phase: A: water (ammonium bicarbonate), B: acetonitrile; elution gradient: B%: 50%-80% over 9 minutes) to obtain example 2. 1H NMR (400 MHz, DMSO-d6) 8 10.72 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.28 (d, J = 2.0 Hz, 1H), 8.10 - 8.02 (m, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.28 - 7.14 (m, 2H), 5.12 (d, J = 10.4 Hz, 1H), 4.93 - 4.78 (m, 2H), 4.37 (dd, J = 7.6, 10.3 Hz, 1H), 2.90 - 2.70 (m, 1H), 1.75 (t, J = 2.4 Hz, 3H), 1.62 (s, 3H), 0.73 (d, J = 6.4 Hz, 3H); m / z (ESI): [M + H]+ = 512.2. Example 3 F F 1-18 3-1 TIPS — 3-2 F F Example 3 Preparation of compound 3-1 Under a nitrogen atmosphere, compound 1-18 (200 mg, 0.04 mmol) and triethylamine (0.1 mL, 0.65 mmol) were dissolved in 3 mL of dichloromethane. The mixture was stirred at 0°C for 10 minutes, and trifluoromethanesulphonic anhydride (72.3 pL, 0.44 mmol) was added dropwise. After the dropwise addition was completed, the mixture was reacted at 0°C for another 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (petroleum ether : ethyl acetate = 1 : 1) to obtain compound 3-1. m / z (ESI): [M + H]+ = 592.1. Preparation of compound 3-2 Under a nitrogen atmosphere, 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (6.19 mg, 0.01 mmol), cuprous iodide (3.22 mg, 0.02 mmol), and triethylamine (25.66 mg, 0.25 mmol) were sequentially added to a solution of compound 3-1 (50 mg, 0.08 mmol) and triisopropylsilylacetylene (0.1 mL, 0.25 mmol) in 0.5 mL of DMF. The reaction solution was warmed to 100°C and stirred for 6 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered through a short pad of silica gel (washed with ethyl acetate), and the filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was purified by reversed-phase column chromatography (0.1% formic acid system) to obtain compound 3-2. 1H NMR (400 MHz, CDCI3): 6 8.61 (s, 1H), 8.47 (d, J = 5.6 Hz, 1H), 8.18 (dd, J = 2.1, 5.4 Hz, 1H), 7.89 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 4.5 Hz, 1H), 7.18 (d, J = 5.7 Hz, 2H), 5.59 (d, J = 2.9 Hz, 1H), 5.03 (d, J = 11.2 Hz, 1H), 4.32 (dd, J = 8.2, 11.0 Hz, 2H), 2.97 (t, J = 7.6 Hz, 1H), 2.37 (s, 1H), 2.03 (d, J = 6.6 Hz, 1H), 1.68 (s, 3H), 1.10 (s, 18H), 0.87 - 0.81 (m, 3H); m / z (ESI): [M + H]+ = 624.2. Preparation of example 3 Under a nitrogen atmosphere, caesium fluoride (30.38 mg, 0.20 mmol) was added to a solution of compound 3-2 (13 mg, 0.02 mmol) in 0.5 mL of DMF. The reaction solution was stirred at 25°C for 1 hour. After the reaction was completed, the mixture was filtered, and the filtrate was separated and purified by preparative high-performance liquid chromatography (Waters Xbridge 150*25 mm* 5 um; mobile phase: A: water (ammonium bicarbonate), B: acetonitrile; elution gradient: B%: 45% - 75% over 9 minutes) to obtain example 3. 1H NMR (400 MHz, CDCI3): 3 8.67 (s, 1H), 8.48 (d, J = 5.5 Hz, 1H), 8.17 (dd, J = 2.0, 5.4 Hz, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.87 (s, 1H), 7.26 - 7.17 (m, 2H), 5.61 (d, J = 2.3 Hz, 1H), 5.06 (d, J = 11.0 Hz, 1H), 4.27 (dd, J = 7.9, 11.2 Hz, 1H), 3.64 (s, 1H), 2.97 (t, J = 7.6 Hz, 1H), 1.71 (s, 3H), 0.88 - 0.74 (m, 3H); m / z (ESI): [M + H]+ = 468.2. Example 4 F7'W^N A / _____►      Zcsj Z’ H ^ o W / —' N-O      F F Example 4 Preparation of compound 4-2 The synthesis route of compound 4-2 was as follows: Under a nitrogen atmosphere, compound 4-1 (3.00 g, 18.4 mmol) was added dropwise to a solution of 1,2-dibromoethane (14.5 g, 77.2 mmol) and triethylamine (5.60 mL, 40.5 mmol) in 50 mL of DMF. The mixture was stirred at 20°C for 16 hours. After the reaction was completed, the reaction solution was poured into 100 mL of water, and the mixture was extracted with ethyl acetate (50 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (eluting with petroleum ether) to obtain compound 4-2. 1H NMR (400 MHz, DMSO-d6): 5 7.87 (s, 4H), 4.45 (t, J = 6.0 Hz, 2H), 3.77 -3.77 (m, 1H), 3.75 (t, J = 6.0 Hz, 1H). Preparation of compound 4-3 Under a nitrogen atmosphere, compound 4-2 (58.8 mg, 0.22 mmol) was added to a solution of compound 1-18 (100 mg, 0.22 mmol) and potassium carbonate (150 mg, 1.09 mmol) in 2 mL of DMF. The reaction solution was warmed to 60°C and stirred for 6.5 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was purified by reversed-phase column chromatography (0.1% formic acid system) to obtain compound 4-3. 1H NMR (400 MHz,CDCl3): 3 8.75 (s, 1H), 8.35 (d, J = 5.6 Hz, 1H), 8.23 (dd, J = 2.4, 5.6 Hz, 1H), 7.80 (d, J = 2.0 Hz, 2H), 7.70 (s, 4H), 7.25 - 7.17 (m, 1H), 7.02 - 6.92 (m, 1H), 5.82 - 5.71 (m, 1H), 5.00 (d, J = 11.6 Hz, 1H), 4.74 - 4.62 (m, 2H), 4.51 (dd, J = 8.0, 10.4 Hz, 1H), 4.44 - 4.25 (m, 2H), 3.07 - 2.97 (m, 1H), 1.78 (s, 3H), 0.80 (dd, J = 2.0, 5.6 Hz, 3H); m / z (ESI): [M+ H]+ = 649.2. Preparation of compound 4-4 Under a nitrogen atmosphere, hydrazine hydrate (14.2 mg, 0.28 mmol) was added to a solution of compound 4-3 (90.0 mg, 0.14 mmol) in 3 mL of ethanol. The reaction solution was warmed to 65°C and stirred for 1 hour. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was concentrated to obtain compound 4-4. 1H NMR (400 MHz, CDCl3): 3 8.70 - 8.64 (m, 1H), 8.47 (d, J = 5.6 Hz, 1H), 8.13 (dd, J = 2.4, 5.6 Hz, 1H), 7.95 (d, J = 2.0 Hz, 1H), 7.87 - 7.80 (m, 1H), 7.13 -7.06 (m, 1H), 6.99 (d, J = 2.4 Hz, 1H), 5.62 - 5.56 (m, 1H), 5.02 (d, J = 11.2 Hz, 1H), 4.49 - 4.40 (m, 1H), 4.38 - 4.23 (m, 2H), 3.96 - 3.88 (m, 1H), 3.86 - 3.79 (m, 1H), 2.88 - 2.74 (m, 1H), 1.29 - 1.23 (m, 3H), 0.83 - 0.77 (m, 3H). Preparation of example 4 Under a nitrogen atmosphere, pyridinium p-toluenesulphonate (0.27 mg) and paraformaldehyde (6.37 mg, 0.21 mmol) were sequentially added to a solution of compound 4-4 (55 mg, 0.11 mmol) in 3 mL of dichloromethane. The reaction solution was warmed to 40°C and stirred for 4 hours. After the reaction was completed, water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was separated and purified by preparative high-performance liquid chromatography (column model: Waters Xbridge 150*25 mm*5 um; mobile phase: A: water (ammonium bicarbonate), B: acetonitrile; gradient: B%: 48%- 78% over 10 minutes) to obtain example 4. 1H NMR (400 MHz, DMSO- d6): 3 10.69 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.28 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H), 7.84 (dd, J = 2.4, 5.6 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.20 - 7.13 (m, 2H), 7.05 (d, J = 7.6 Hz, 1H), 6.58 (d, J = 7.6 Hz, 1H), 5.12 (d, J = 10.6 Hz, 1H), 4.43 (dd, J = 4.8, 6.8 Hz, 1H), 4.37 - 4.23 (m, 4H), 2.88 - 2.76 (m, 1H), 1.60 (s, 3H), 0.70 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ = 531.2. Example 5 5-3                           Example 5 Preparation of compound 5-2 The synthesis route of compound 5-2 was as follows: HO         Cl TBSCI, imidazole TBSO         Cl \ = / ---------\ = / 5-1                                       5-2 Under a nitrogen atmosphere, tert-butyl dimethylsilyl chloride (865 mg, 5.74 mmol) was added to a solution of compound 5-1 (300 mg, 2.87 mmol) and imidazole (586 mg, 8.61 mmol) in 5 mL of DMF. The reaction solution was stirred at 20°C for 3 hours. After the reaction was completed, water (50 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (25 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (eluting with petroleum ether) to obtain compound 5-2. 1H NMR (400 MHz, CDCI3): 8 4.37 (t, J = 2.0 Hz, 2H), 4.18 (t, J = 2.0 Hz, 2H), 0.92 (s, 9H), 0.13 (s, 6H). Preparation of compound 5-3 Under a nitrogen atmosphere, a solution of compound 5-2 (28.6 mg, 0.13 mmol) in DMF (1 mL) was slowly added to a suspension of compound 1-18 (60 mg, 0.13 mmol) and potassium carbonate (90.3 mg, 0.65 mmol) in DMF (1 mL). The reaction solution was warmed to 60°C and stirred for 2 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was separated and purified by reversed-phase preparative chromatography (mobile phase A: water (0.1% aqueous ammonia), B: acetonitrile; elution gradient: B%: 100% over 3 minutes) to obtain compound 5-3. 1H NMR (400 MHz, DMSO-d6): 5 10.73 (s, 1H), 8.48 (d, J = 5.6 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.05 (d, J = 2.4 Hz, 1H), 7.95 (s, 4H), 7.84 (dd, J = 2.4, 5.6 Hz, 1H), 7.61 (d, J = 2.4 Hz, 1H), 7.26 - 7.17 (m, 2H), 5.12 (d, J = 10.4 Hz, 1H), 5.04 -4.92 (m, 2H), 4.33 (dd, J = 7.6, 10.2 Hz, 1H), 4.28 - 4.22 (m, 2H), 1.61 (s, 3H), 0.77 (s, 9H), -0.06 (s, 6H); m / z (ESI): [M+ H]+ = 642.3. Preparation of example 5 Compound 5-3 (25 mg, 0.04 mmol) was dissolved in a solution of hydrogen chloride in methanol (2 mL, 2 mol / L), and the mixture was stirred at 25°C for 0.5 hours. After the reaction was completed, the mixture was concentrated, diluted with 2 mL of methanol, and adjusted to pH = 8 with aqueous ammonia. The resulting mixture was separated and purified by preparative high-performance liquid chromatography (column model: Waters Xbridge 150*25 mm*5 um; mobile phase: A: water (ammonium bicarbonate), B: acetonitrile; elution gradient: B%: 38%-68% over 9 minutes) to obtain example 5. 1H NMR (400 MHz, DMSO-d6): S 10.73 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.63 (br d, J = 1.6 Hz, 1H), 7.28 - 7.14 (m, 2H), 5.21 (t, J = 6.0 Hz, 1H), 5.11 (d, J = 10.4 Hz, 1H), 4.94 (d, J = 1.6 Hz, 2H), 4.34 (dd, J = 7.6, 10.4 Hz, 1H), 4.10 - 4.03 (m, 2H), 2.90 - 2.79 (m, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.4 Hz, 3H); m / z (ESI): [M+ H]+ = 528.2. Example 6 Example 6 Preparation of compound 6-2 Under a nitrogen atmosphere, methyllithium (5.3 mL, 8.41 mmol) was slowly added dropwise to a solution of compound 6-1 (1.0 g, 8.41 mmol) in 15 mL of tetrahydrofuran at -78°C. The reaction solution was stirred at -78°C for 5 minutes, and then acetone (6.2 mL, 84.06 mmol) was slowly added dropwise. After the dropwise addition was completed, the reaction solution was stirred at -78°C for another 10 minutes. After the reaction was completed, the reaction solution was quenched with 30 mL of saturated aqueous ammonium chloride solution. The aqueous phase was extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, filtered, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 10:1) to obtain compound 6-2. 1H NMR (400 MHz, CDCI3): S 3.94 (s, 2H), 1.53 (s, 6H). Preparation of example 6 Under a nitrogen atmosphere, potassium carbonate (63.18 mg, 0.46 mmol) and compound 6-2 (16.29 mg, 0.09 mmol) were added to a solution of compound 1-18 (50 mg, 0.09 mmol) in 1 mL of DMF. The reaction solution was stirred at 60°C for 2 hours. After the reaction was completed, the mixture was filtered, and the filtrate was purified by preparative high-performance liquid chromatography (column model: Waters Xbridge 150* 25 mm *5 um; mobile phase: A: water (ammonium bicarbonate), B: acetonitrile; elution gradient: B%: 35%-65% over 10 minutes) to obtain example 6. 1H NMR (400 MHz, DMSO- d6): S 10.74 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 2.0 Hz, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.61 (d, J = 1.6 Hz, 1H), 7.24 - 7.15 (m, 2H), 5.31 (s, 1H), 5.12 (d, J = 10.6 Hz, 1H), 4.94 (s, 2H), 4.28 (dd, J = 7.2, 10.2 Hz, 1H), 2.85 (t, J = 7.2 Hz, 1H), 1.63 (s, 3H), 1.27 (s, 3H), 1.24 (s, 3H), 0.74 (d, J = 5.6 Hz, 3H); m / z (ESI): [M + H]+ = 556.3. Example 7 Example 7 Under a nitrogen atmosphere, 2-methyl-3-butyn-2-ol (0.1 mL, 0.89 mmol) and K2CO3 (451.27 mg, 3.27 mmol) were sequentially added to a solution of compound 1-18 (300 mg, 0.65 mmol) in DMF (6 mL). The reaction solution was reacted at 100°C for 2 hours, and then additional compound 2 (0.1 mL, 0.89 mmol) was added. The reaction solution was reacted at 100°C for another 2 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was purified by reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x 5 um; water (water (NH4HCO3), ACN, 52% - 82%, 16 min) to obtain example 7. 1H NMR (400 MHz, DMSO- d6): 3 10.76 (br s, 1H),8.48 (d, J = 5.52 Hz, 1H), 8.25 (d, J = 1.88 Hz, 1H), 8.08 (d, J = 2.00 Hz, 1H), 7.82 (dd, J = 5.40, 1.88 Hz, 1H), 7.63 (br s, 1H), 7.16 - 7.29 (m, 2H), 5.09 (d, J = 10.52 Hz, 1H), 4.43 (dd, J = 10.32, 7.60 Hz, 1H), 3.54 (s, 1H), 2.80 (t, J = 7.20 Hz, 1H), 1.70 (s, 3H), 1.67 (s, 3H), 1.61 (s, 3H), 0.70 (br d, J = 5.12 Hz, 3H); m / z (ESI): [M+ H]+ = 526.1. Example 8 8-1              8-2                              Example 8 Preparation of compound 8-2 Under a nitrogen atmosphere, methanesulphonic anhydride (0.80 mL, 6.42 mmol) was slowly added to a solution of compound 8-1 (300 mg, 4.28 mmol) and triethylamine (1.8 mL, 12.8 mmol) in dichloromethane (5 mL). The reaction solution was stirred at 20°C for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, diluted with water (50 mL), and extracted with ethyl acetate (25 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain compound 8-2. 1H NMR (400 MHz, CDCl3): 3 5.30 (dq, J = 2.0, 6.8 Hz, 1H), 3.13 (s, 3H), 2.71 (d, J = 2.0 Hz, 1H), 1.67 (d, J = 6.8 Hz, 3H). Preparation of example 8 Under a nitrogen atmosphere, a solution of compound 8-2 (6.45 mg, 0.04 mmol) in DMF (0.5 mL) was slowly added to a solution of compound 1-18 (100 mg, 0.22 mmol) and potassium carbonate (150 mg, 1.09 mmol) in DMF (0.5 mL). The reaction solution was stirred at 60°C for 16 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was purified by reversed-phase preparative chromatography (column: Waters Xbridge 150 x 25 mm x 5 um; water (NH4HCO3), ACN, 40%-70%, 15 min) to obtain example 8. 1H NMR (400 MHz, DMSO- d6): S 10.70 (s, 1H), 8.48 (d, J = 5.6 Hz, 1H), 8.25 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 2.0, 5.6 Hz, 1H), 7.62 (br d, J = 2.0 Hz, 1H), 7.27 - 7.14 (m, 2H), 5.25 (dq, J = 2.0, 6.4 Hz, 1H), 5.10 (d, J = 10.8 Hz, 1H), 4.31 (dd, J = 7.6, 10.8 Hz, 1H), 3.67 (d, J = 2.0 Hz, 1H), 2.85 - 2.73 (m, 1H), 1.66 - 1.57 (m, 6H), 0.77 (br d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ =512.2. Example 9 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (132.4 mg, 0.55 mmol) and (S)-(-)-3-butyn-2-ol (38.45 mg, 0.55 mmol) were added to a solution of compound 1-18 (60 mg, 0.11 mmol) in 1,4-dioxane (2 mL). The reaction solution was stirred at 40°C for 16 hours. After the reaction was completed, the reaction solution was quenched with water (40 mL) and extracted with ethyl acetate (30 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified and separated by reversed-phase preparative chromatography (Column: Waters Xbridge 150 x 25 mm x 5 um; Condition: water (NH4HCO3)-ACN; Begin B:43, End B:73; Gradient Time (min): 10; 100%B Hold Time (min):4, Flow Rate (ml / min): 25) to obtain example 9. 1H NMR (400 MHz, DMSO- d6): 5 10.72 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.63 (br s, 1H), 7.30 - 7.15 (m, 2H), 5.16 - 5.06 (m, 2H), 4.45 (dd, J = 7.2, 10.2 Hz, 1H), 3.41 (d, J = 2.0 Hz, 1H), 2.91 - 2.79 (m, 1H), 1.66 - 1.59 (m, 6H), 0.70 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H] + = 512.1. Example 10 Preparation of compound 10-2 Under a nitrogen atmosphere, tert-butyl dimethylsilyl chloride (1.92 g, 12.80 mmol) was added to a solution of compound 10-1 (0.50 mL, 6.40 mmol) and imidazole (1.31 g, 19.2 mmol) in DMF (10 mL). The reaction solution was stirred at 20°C for 16 hours. After the reaction was completed, the reaction solution was quenched with water (100 mL) and extracted with ethyl acetate (50 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated and purified by column chromatography (eluting with petroleum ether) to obtain compound 10-2. 1H NMR (400 MHz,CDCl3): S 3.74 (t, J = 6.4 Hz, 2H), 2.68 - 2.59 (m, 2H), 1.57 (s, 1H), 0.93 - 0.90 (m, 9H), 0.10 - 0.07 (m, 6H). Preparation of compound 10-3 Under a nitrogen atmosphere, tris(dibenzylideneacetone)dipalladium (31.0 mg, 0.03 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (39.1 mg, 0.07 mmol) were added to a solution of compound 3-1 (200 mg, 0.34 mmol), compound 10-2 (130 mg, 0.68 mmol), and N,N- diisopropylethylamine (0.3 mL, 2.03 mmol) in 1,4-dioxane (4 mL). The reaction solution was stirred at 100°C for 16 hours. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with water (50 mL), and extracted with ethyl acetate (20 mL x 2). The combined organic phases were washed with sodium chloride aqueous solution (20 mL), subjected to liquid separation, and then dried over anhydrous sodium sulphate, filtered, and concentrated to obtain a crude product, which was separated and purified by column chromatography (petroleum ether / ethyl acetate = 10 / 1 to 2 / 1) to obtain compound 10-3. 1H NMR (400 MHz,CDCl3): d = 8.71 (s, 1H), 8.46 (d, J = 5.6 Hz, 1H), 8.16 (dd, J = 2.0, 5.6 Hz, 1H), 7.95 (d, J = 2.0 Hz, 1H), 7.85 (d, J = 4.0 Hz, 1H), 7.24 -7.16 (m, 2H), 5.66 (d, J = 3.6 Hz, 1H), 5.06 (d, J = 11.2 Hz, 1H), 4.54 (dd, J = 8.0, 11.2 Hz, 1H), 3.73 - 3.65 (m, 2H), 3.15 (dq, J = 4.8, 7.2 Hz, 3H), 3.04 - 2.95 (m, 2H), 2.83 (m, 1H), 0.81 (s, 9H), 0.78 - 0.73 (m, 3H), 0.04 (d, J = 10.0 Hz, 6H); m / z(ESI): [M+ H]+ = 634.1. Preparation of example 10 Under a nitrogen atmosphere, compound 10-3 (95 mg, 0.15 mmol) was added to a solution of hydrogen chloride in methanol (2 N, 5 mL). The reaction solution was reacted at 17°C for 0.5 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue was diluted with methanol (2 mL). The mixture was adjusted to pH=8 with aqueous ammonia, and then separated and purified by reversed-phase preparative chromatography (column: Waters Xbridge 150*25 mm* 5 um; water (NH4HCO3)-ACN, 38%-68%, 15 min) to obtain example 10. 1HNMR (400 MHz, DMSO- d6): 5 10.68 (s, 1H), 8.48 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.09 - 8.03 (m, 1H), 7.83 (dd, J = 2.4, 5.6 Hz, 1H), 7.62 (br d, J = 2.0 Hz, 1H), 7.55 - 7.43 (m, 1H), 7.29 (dd, J = 5.2, 8.0 Hz, 1H), 5.17 (d, J = 10.4 Hz, 1H), 4.84 (t, J = 5.6 Hz, 1H), 4.69 (dd, J = 7.6, 10.4 Hz, 1H), 3.51 - 3.39 (m, 2H), 2.96 - 2.89 (m, 2H), 2.84 (t, J = 7.2 Hz, 1H), 1.64 (s, 3H), 0.70 (br d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ = 520.2. Example 11 Preparation of compound 11-2 Under a nitrogen atmosphere, triethylamine (223.8 pL, 1.61 mmol) and 11-1 (81.67 mg, 0.54 mmol) were sequentially added to a solution of compound 1-15 (200 mg, 0.54 mmol) in 4 mL of dichloromethane. The reaction solution was stirred at 25°C for 1 hour. After the reaction was completed, the mixture was concentrated to obtain a crude product, which was purified and separated by reversed-phase preparative chromatography (0.1% FA) to obtain compound 11-2. m / z (ESI): [M + H]+ = 489.1. Preparation of compound 11-3 Under a nitrogen atmosphere, boron tribromide (0.1 mL, 0.24 mmol) was slowly added dropwise to a solution of compound 11-2 (80 mg, 0.16 mmol) in dichloromethane (2 mL) at 0°C. The reaction solution was stirred at 25°C for 1.5 hours. After the reaction was completed, the reaction solution was diluted with 3 mL of dichloromethane, quenched by dropwise addition of 4 mL of saturated aqueous sodium bicarbonate solution, and extracted with dichloromethane (5 mL x 3). The combined organic phases were washed with 20 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified and separated by reversed-phase preparative chromatography (0.1% FA) to obtain 11-3. LC-MS (ESI): [M + H] + =475.1. Preparation of example 11 Under a nitrogen atmosphere, 3-bromopropyne (12.54 mg, 0.11 mmol) was added to a solution of compound 11-3 (50 mg, 0.11 mmol) and K2CO3 (72.82 mg, 0.53 mmol) in 1 mL of N,N-dimethylformamide. The reaction solution was reacted at 60°C for 2 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was purified by reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x 5 um; water (water (NH4HCO3), ACN, 45% - 75% over 10 min) to obtain example 11. 1H NMR (400 MHz, DMSO- d6): J 10.54 (s, 1H), 8.34 (d, J = 5.52 Hz, 1H), 7.86 (d, J = 1.88 Hz, 1H), 7.49 (dd, J = 5.52, 2.12 Hz, 1H), 7.11 - 7.28 (m, 2H), 5.18 (s, 1H), 5.09 (d, J = 10.52 Hz, 1H), 4.86 - 4.99 (m, 2H), 4.33 (dd, J = 10.36, 7.52 Hz, 1H), 3.65 (t, J = 2.36 Hz, 1H), 2.84 (t, J = 7.44 Hz, 1H), 1.60 (s, 3H), 1.39 (s, 6H), 0.73 (d, J = 6.36 Hz, 3H); m / z (ESI): [M+ H]+ = 513.1. Example 12 Preparation of compound 12-2 Under a nitrogen atmosphere, deuterated lithium aluminium hydride (2.6 mL, 5.12 mmol, 2 M in THF) was slowly added dropwise to a solution of compound 12-1 (1 g, 6.40 mmol) in 40 mL of tetrahydrofuran at 0°C. The reaction solution was stirred at 0°C for 1 hour. After the reaction was completed, the reaction solution was quenched with 1 mL of deuterium oxide, dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified and separated by column chromatography (petroleum ether : ethyl acetate = 10 : 1) to obtain compound 12-2. 1H NMR (400 MHz, CDCI3): J 1.67 (s, 1H), 0.20 - 0.17 (m, 9H). Preparation of compound 12-3 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (176.54 mg, 0.77 mmol) and compound 12-2 (95.28 mg, 0.73 mmol) were sequentially added to a solution of compound 1-18 (80 mg, 0.15 mmol) in 2 mL of dioxane. The reaction solution was stirred at 40°C for 16 hours. After the reaction was completed, the reaction solution was quenched with 10 mL of water and extracted with ethyl acetate (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified and separated by silica gel column chromatography (petroleum ether : ethyl acetate = 2 : 1) to obtain compound 12-3. 1H NMR (400 MHz, CDCl3): J 8.71 - 8.67 (m, 1H), 8.47 (d, J = 5.6 Hz, 1H), 8.18 (dd, J = 2.0, 5.6 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.88 (br d, J = 2.0 Hz, 1H), 7.17 - 7.11 (m, 1H), 6.99 - 6.93 (m, 1H), 5.62 - 5.56 (m, 1H), 5.04 (d, J = 11.2 Hz, 1H), 4.18 (dd, J = 6.8, 10.8 Hz, 1H), 2.91 (t, J = 7.6 Hz, 1H), 1.72 (s, 3H), 0.84 -0.80 (m, 3H), 0.09 (s, 9H); m / z (ESI): [M + H]+ = 572.2. Preparation of example 12 Under a nitrogen atmosphere, tetrabutylammonium fluoride (235 pL, 0.23 mmol, 1 M in THF) was added to a solution of compound 12-3 (60 mg, 0.08 mmol) in 2 mL of tetrahydrofuran. The reaction solution was stirred at 22.5°C for 1.5 hours. After the reaction was completed, the reaction solution was quenched with 40 mL of water and extracted with ethyl acetate (20 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified and separated by reversed-phase preparative chromatography (Column: Waters Xbridge 150 x 25 mm x 5 um; Condition: water (NH4HCO3)-ACN; Begin B:43, End B:73; Gradient Time (min): 10; 100%B Hold Time (min):4, Flow Rate (ml / min): 25) to obtain example 12. 1H NMR (400 MHz, DMSO- d6): 6 10.71 (br s, 1H), 8.48 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 2.0 Hz, 1H), 7.83 (dd, J = 2.0, 5.6 Hz, 1H), 7.61 (d, J = 2.0 Hz, 1H), 7.28 - 7.15 (m, 2H), 5.11 (d, J = 10.2 Hz, 1H), 4.33 (dd, J = 7.2, 10.2 Hz, 1H), 3.63 (s, 1H), 2.90 - 2.78 (m, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.8 Hz, 3H); m / z (ESI): [M + H]+ = 500.1. Example 13 Under a nitrogen atmosphere, 4-bromo-1-butyne (193.81 mg, 1.46 mmol) and potassium carbonate (225.64 mg, 1.63 mmol) were sequentially added to a solution of compound 1-18 (150 mg, 0.33 mmol) in 3 mL of DMF. The reaction solution was reacted at 80°C for 16 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was purified by reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x 5 um; water (water (NH4HCO3), ACN, 48% - 78%, 25 min) to obtain example 13. 1H NMR (400 MHz, DMSO- d6): 6 10.69 (s, 1H), 8.49 (d, J = 5.52 Hz, 1H), 8.28 (d, J = 2.00 Hz, 1H), 8.06 (s, 1H), 7.84 (dd, J = 5.56, 2.20 Hz, 1H), 7.62 (d, J = 2.24 Hz, 1H), 7.23 - 7.13 (m, 2H), 5.12 (d, J = 10.52 Hz, 1H), 4.35 (dd, J = 10.28, 7.64 Hz, 1H), 4.30 - 4.23 (m, 1H), 4.20 - 4.13 (m, 1H), 2.89 - 2.87 (m, 1H), 2.69 -2.65 (m, 2H), 2.47 - 2.43 (m, 1H), 1.63 (s, 3H), 0.72 (d, J = 6.76Hz, 3H); m / z (ESI): [M+ H]+ =512.1. Example 14 °—OH 14-2 Example 14 Preparation of compound 14-2 Under a nitrogen atmosphere, sodium hydride (14.5 mg, 0.36 mmol) was slowly added to a solution of compound 14-1 (0.4 mL, 8.06 mmol) in 5 mL of DMF at 0°C. The reaction solution was stirred at 0°C for half an hour, and then bromopropyne (642 mg, 5.40 mmol) was added dropwise. After the dropwise addition was completed, the reaction solution was warmed to 50°C and stirred for another 16 hours. After the reaction was completed, the reaction solution was quenched by dropwise addition to ice-cold saturated ammonium chloride (0.0 mL), and extracted with ethyl acetate (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2 / 1) to obtain compound 14-2. 1H NMR (400 MHz, DMSO- d6): 3 4.65 (t, J = 5.4 Hz, 1H), 4.13 (d, J = 2.4 Hz, 2H), 3.53 - 3.47 (m, 2H), 3.47 - 3.43 (m, 2H), 3.41 (t, J = 2.4 Hz, 1H). Preparation of example 14 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (131 mg, 0.54 mmol) was added to a solution of compound 1-18 (50.0 mg, 0.11 mmol) and compound 14-2 (54.5 mg, 0.54 mmol) in 2 mL of dioxane. The reaction solution was warmed to 40°C and reacted for 2 hours. After the reaction was completed, the reaction solution was quenched with 50 mL of water and extracted with ethyl acetate (20 mL*2). The combined organic phases were washed with sodium chloride aqueous solution (20 mL), and subjected to liquid separation. The aqueous phase was extracted once more with ethyl acetate (20 mL). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure. The crude product was purified by reversed-phase preparative chromatography (column: Waters Xbridge 150 x 25 mm x 5 um; water (NH4HCO3), ACN, 40%-70%, 15 min) to obtain example 14. 1H NMR (400 MHz, DMSO- d6): 8 10.70 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.22 - 7.12 (m, 2H), 5.11 (d, J = 10.8 Hz, 1H), 4.36 - 4.27 (m, 2H), 4.27 - 4.21 (m, 1H), 4.19 (t, J = 2.4 Hz, 2H), 3.75 (td, J = 2.8, 5.2 Hz, 2H), 3.44 (t, J = 2.4 Hz, 1H), 2.91 - 2.80 (m, 1H), 1.62 (s, 3H), 0.71 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ =542.2. Example 15 F F 15-1                         15-2                                   Example 15 Preparation of compound 15-2 Under a nitrogen atmosphere, n-butyllithium (6.8 mL, 17.12 mmol, 2.5 M) was slowly added dropwise to a solution of compound 15-1 (1 g, 14.27 mmol) in tetrahydrofuran (10 mL) at -78°C. The reaction solution was stirred at -78°C for 1 hour, and then paraformaldehyde (2.06 g, 22.83 mmol) was added. The reaction solution was slowly warmed to 25°C and stirred for 16 hours. After the reaction was completed, the reaction solution was cooled to 0°C, quenched with saturated aqueous ammonium chloride solution (50 mL), and extracted with ethyl acetate (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (petroleum ether / ethyl acetate = 2 / 1) to obtain compound 15-2. 1H NMR (400 MHz, DMSO-d6): 8 5.19 (t, J = 5.2 Hz, 1H), 4.12 - 4.08 (m, 4H), 3.25 (s, 3H). Preparation of example 15 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (116.90 mg, 0.48 mmol) and compound 15-2 (48.49 mg, 0.48 mmol) were sequentially added to a solution of compound 1-18 (50 mg, 0.10 mmol) in dioxane (2 mL). The reaction solution was stirred at 40°C for 12 hours. After the reaction was completed, the reaction solution was quenched with water (40 mL) and extracted with ethyl acetate (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified and separated by reversed-phase preparative chromatography (Column: Waters Xbridge 150 x 25 mm x 5 um; water (NH4HCO3)-ACN; Begin B:40, End B:70; Gradient Time (min): 10; 100%B Hold Time (min):4, Flow Rate (ml / min): 25) to obtain example 15. 1H NMR (400 MHz, DMSO-d6): £ 10.72 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.28 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.4 Hz, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.62 (d, J = 2.4 Hz, 1H), 7.28 - 7.15 (m, 2H), 5.12 (d, J = 10.4 Hz, 1H), 5.06 - 4.93 (m, 2H), 4.34 (dd, J = 7.2, 10.4 Hz, 1H), 4.12 - 4.01 (m, 2H), 3.13 (s, 3H), 2.88 - 2.80 (m, 1H), 1.61 (s, 3H), 0.73 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ = 542.2. Example 16 Example 16 Preparation of compound 16-2 Under a nitrogen atmosphere, tert-butyldiphenylchlorosilane (21.57 g, 78.47 mmol) was added to a solution of compound 16-1 (5 g, 71.34 mmol), 4-dimethylaminopyridine (0.87 g, 7.13 mmol) and triethylamine (19.8 mL, 142.67 mmol) in dichloromethane (50 mL) at 0°C. The reaction solution was warmed to 25°C and stirred for 12 hours. After the reaction was completed, the reaction was quenched with saturated aqueous ammonium chloride solution (50 mL), and the aqueous phase was extracted with dichloromethane (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 16-2. 1H NMR (400 MHz, CDCI3): 3 7.77 (td, J = 1.3, 7.9 Hz, 2H), 7.70 (td, J = 1.3, 7.9 Hz, 2H), 7.51 - 7.37 (m, 6H), 4.53 - 4.42 (m, 1H), 2.35 (dd, J = 0.6, 2.0 Hz, 1H), 1.41 (dd, J = 0.9, 6.4 Hz, 3H), 1.10 (d, J = 1.0 Hz, 9H). Preparation of compound 16-3 Under a nitrogen atmosphere, a solution of methyllithium in diethyl ether (15.2 mL, 24.31 mmol, 1.6 M) was slowly added dropwise to a solution of compound 16-2 (5 g, 16.21 mmol) in tetrahydrofuran (100 mL) at -70°C. The reaction solution was stirred at -70°C for 1 hour, and then paraformaldehyde (0.73 g, 24.31 mmol) was added portionwise to the reaction solution. The mixed solution was warmed to 22°C and stirred for 12 hours. After the reaction was completed, the reaction solution was cooled to 0°C, and quenched by dropwise addition of saturated aqueous ammonium chloride solution (50 mL). The aqueous phase was extracted with ethyl acetate (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated to dryness under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 16-3. 1H NMR (400 MHz, CDCl3): 3 7.76 (d, J = 6.6 Hz, 2H), 7.70 (d, J = 6.5 Hz, 2H), 7.48 - 7.35 (m, 6H), 4.54 (q, J = 6.4 Hz, 1H), 4.10 - 4.06 (m, 2H), 1.42 (d, J = 6.5 Hz, 3H), 1.21 - 1.14 (m, 1H), 1.08 (s, 9H). Preparation of compound 16-4 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (236.44 mg, 0.98 mmol) was added to a solution of 1-18 (150 mg, 0.33 mmol) and compound 16-3 (1105.38 mg, 3.27 mmol) in 1,4-dioxane (1.5 mL). The reaction solution was stirred at 25°C for 12 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was purified by reversed-phase column chromatography (0.1% formic acid system) to obtain compound 16-4. 1H NMR (400 MHz, CDCl3): 3 8.69 (s, 1H), 8.42 (d, J = 5.6 Hz, 1H), 8.14 (dd, J = 2.1, 5.5 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.89 - 7.84 (m, 1H), 7.68 (dd, J = 1.5, 7.9 Hz, 2H), 7.61 (dd, J = 1.3, 7.9 Hz, 2H), 7.45 - 7.32 (m, 7H), 7.15 - 7.08 (m, 1H), 7.00 - 6.90 (m, 1H), 5.65 (d, J = 4.1 Hz, 1H), 5.01 (d, J = 11.3 Hz, 1H), 4.76 (q, J = 15.1 Hz, 2H), 4.42 (q, J = 6.5 Hz, 1H), 2.89 - 2.78 (m, 1H), 1.64 (s, 3H), 1.29 - 1.27 (m, 3H), 1.01 (s, 9H), 0.82 - 0.77 (m, 3H); m / z (ESI): [M + H]+ = 780.2. Preparation of example 16 Under a nitrogen atmosphere, ammonium fluoride (189.98 mg, 5.13 mmol) was added to a solution of compound 16-4 (200 mg, 0.26 mmol) in methanol (4 mL). The reaction solution was stirred at 25°C for 12 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was purified by reversed-phase preparative chromatography (Phenomenex luna C18 150 x 40 mm x 15 um; mobile phase: water (FA), ACN; B%: 42% - 72%, 15 min) to obtain example 16. 1H NMR (400 MHz, DMSO-d6): 8 10.72 (s, 1H), 8.49 (d, J = 5.4 Hz, 1H), 8.27 (d, J = 1.9 Hz, 1H), 8.07 (d, J = 2.1 Hz, 1H), 7.84 (dd, J = 2.2, 5.6 Hz, 1H), 7.62 (d, J = 2.3 Hz, 1H), 7.27 - 7.14 (m, 2H), 5.32 (d, J = 5.4 Hz, 1H), 5.12 (d, J = 10.5 Hz, 1H), 4.93 (s, 2H), 4.40 - 4.22 (m, 2H), 2.90 - 2.81 (m, 1H), 1.62 (s, 3H), 1.20 (d, J = 6.5 Hz, 3H), 0.74 (d, J = 6.6 Hz, 3H); m / z (ESI): [M + H]+ = 542.2. Example 17 Example 17 Preparation of compound 17-2 Under a nitrogen atmosphere, tert-butyldiphenylchlorosilane (8.63 g, 31.39 mmol) was added to a solution of compound 17-1 (2 g, 28.53 mmol), 4-dimethylaminopyridine (0.35 g, 2.85 mmol) and triethylamine (7.9 mL, 57.07 mmol) in dichloromethane (20 mL) at 0°C. The reaction solution was stirred at 25°C for 12 hours. After the reaction was completed, the reaction was quenched with saturated aqueous ammonium chloride solution (20 mL), and the aqueous phase was extracted with dichloromethane (15 mL*3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated to dryness under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 17-2. 1H NMR (400 MHz, CDCI3): 8 7.77 (dd, J = 1.3, 7.8 Hz, 2H), 7.73 - 7.68 (m, 2H), 7.48 - 7.36 (m, 6H), 4.47 (dq, J = 2.0, 6.5 Hz, 1H), 2.35 (d, J = 2.1 Hz, 1H), 1.41 (d, J = 6.5 Hz, 3H), 1.10 (s, 9H). Preparation of compound 17-3 Under a nitrogen atmosphere, a solution of methyllithium in diethyl ether (4.9 mL, 7.78 mmol, 1.6 M) was slowly added dropwise to a solution of compound 17-2 (1.6 g, 5.19 mmol) in tetrahydrofuran (30 mL) at -70°C. The reaction solution was stirred at -70°C for 1 hour, and then paraformaldehyde (0.47 g, 15.56 mmol) was added portionwise to the reaction solution. The mixed solution was warmed to 27°C and stirred for 12 hours. After the reaction was completed, the reaction solution was cooled to 0°C, and the reaction was quenched by dropwise addition of saturated aqueous ammonium chloride solution (15 mL). The aqueous phase was extracted with ethyl acetate (20 mL*3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated to dryness under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 17-3. 1H NMR (400 MHz, CDCl3): 8 7.77 (dd, J = 1.1, 7.6 Hz, 2H), 7.73 - 7.68 (m, 2H), 7.49 - 7.35 (m, 6H), 4.60 - 4.50 (m, 1H), 4.09 (d, J = 1.4 Hz, 2H), 1.42 (d, J = 6.5 Hz, 3H), 1.08 (s, 9H). Preparation of compound 17-4 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (157.62 mg, 0.65 mmol) was added to a solution of 1-18 (100 mg, 0.22 mmol) and compound 17-3 (736.92 mg, 2.18 mmol) in 1,4-dioxane (1 mL). The reaction solution was stirred at 25°C for 12 hours. The reaction solution was filtered, and the filtrate was purified by reversed-phase column chromatography (0.1% formic acid system) to obtain compound 17-4. 1H NMR (400 MHz, CDCI3): J 8.61 (s, 1H), 8.36 (d, J = 5.6 Hz, 1H), 8.08 (dd, J = 2.2, 5.6 Hz, 1H), 7.85 (d, J = 2.0 Hz, 1H), 7.84 - 7.79 (m, 1H), 7.61 (dd, J = 1.3, 7.9 Hz, 2H), 7.58 - 7.52 (m, 2H), 7.39 - 7.23 (m, 7H), 7.09 - 7.02 (m, 1H), 6.94 -6.83 (m, 1H), 5.56 (br d, J = 3.5 Hz, 1H), 4.94 (d, J = 11.3 Hz, 1H), 4.80 - 4.58 (m, 2H), 4.35 (q, J = 6.5 Hz, 1H), 2.79 - 2.67 (m, 1H), 1.55 (s, 3H), 1.20 (s, 3H), 0.95 (s, 9H), 0.70 (dd, J = 1.9, 5.3 Hz, 3H); m / z (ESI): [M + H]+ = 780.3. Preparation of example 17 Under a nitrogen atmosphere, ammonium fluoride (132.98 mg, 3.59 mmol) was added to a solution of compound 17-4 (140 mg, 0.18 mmol) in methanol (3 mL). The reaction solution was stirred at 25°C for 12 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was purified by reversed-phase preparative chromatography (Phenomenex luna C18 150*25 mm* 10 um; mobile phase: water (FA), ACN; B%: 42% - 72%, 15 min) to obtain example 17. 1H NMR (400 MHz, DMSO-d6): J 10.73 (s, 1H), 8.49 (d, J = 5.5 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 2.1 Hz, 1H), 7.84 (dd, J = 2.1, 5.5 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.28 - 7.15 (m, 2H), 5.32 (d, J = 5.4 Hz, 1H), 5.12 (d, J = 10.5 Hz, 1H), 4.94 (s, 2H), 4.40 - 4.23 (m, 2H), 2.90 - 2.79 (m, 1H), 1.63 (s, 3H), 1.15 (d, J = 6.6 Hz, 3H), 0.74 (d, J = 6.1 Hz, 3H); m / z (ESI): [M + H]+ = 542.1. Example 18 18-1                      18-2                                 Example 18 Preparation of compound 18-2 Under a nitrogen atmosphere, deuterated lithium aluminium hydride (0.34 g, 8.15 mmol) was slowly added portionwise to a solution of compound 18-1 (1 g, 10.19 mmol) in diethyl ether (15 mL) at 0°C. The reaction solution was stirred at 0°C for 1 hour. The reaction was quenched with deuterium oxide (1 mL) to the reaction solution, and the mixture was dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified and separated by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 18-2. 1H NMR (400 MHz, CDCI3): S 1.85 (s, 3H). Preparation of example 18 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (231.18 mg, 0.96 mmol) and compound 18-2 (138.12 mg, 1.92 mmol) were added to a solution of compound 1-18 (100 mg, 0.19 mmol) in dioxane (1 mL). The reaction solution was warmed to 40°C and stirred for 16 hours. After the reaction was completed, the reaction was quenched with water (30 mL) and extracted with ethyl acetate (30 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified and separated by reversed-phase preparative chromatography (Column: Waters Xbridge 150 x 25 mm x 5 um; Condition: water (NH4HCO3)-ACN; Begin B:43, End B:73; Gradient Time (min): 15; 100%B Hold Time (min):4, Flow Rate (ml / min): 25) to obtain example 18. 1H NMR (400 MHz, DMSO-d6): S 10.72 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.28 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 2.0 Hz, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.28 - 7.14 (m, 2H), 5.12 (d, J = 10.8 Hz, 1H), 4.37 (dd, J = 7.2, 10.8 Hz, 1H), 2.90 - 2.79 (m, 1H), 1.75 (s, 3H), 1.62 (s, 3H), 0.73 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H]+ = 514.1. Example 19 Preparation of compound 19-2 Under a nitrogen atmosphere, n-butyllithium (14.1 mL, 35.2 mmol, 2.5 M) was slowly added dropwise to a solution of compound 19-1 (5.00 g, 29.4 mmol) in tetrahydrofuran (150 mL) at -40°C. The reaction solution was stirred at -40°C for 0.5 hours, and then chloroformate (3.3 mL, 43.2 mmol) was added dropwise. The mixed solution was stirred at -40°C for another 2 hours. The reaction solution was slowly added dropwise to saturated aqueous ammonium chloride solution (50 mL) that had been pre-cooled to 0°C. The aqueous phase was extracted with ethyl acetate (150 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 50 / 1) to obtain compound 19-2. 1H NMR (400 MHz, CDCI3): S 4.44 (s, 2H), 3.79 (s, 3H), 0.92 (s, 9H), 0.14 (s, 6H). Preparation of compound 19-3 Under a nitrogen atmosphere, deuterated lithium aluminium hydride (0.29 g, 7.01 mmol) was slowly added portionwise to a solution of compound 19-2 (2.00 g, 8.76 mmol) in tetrahydrofuran (100 mL) at -70°C. The mixed solution was stirred at -70°C for 2 hours, warmed to 0°C, and then quenched by slow dropwise addition of deuterium oxide (1 mL). The mixture was stirred for 10 minutes, warmed to 25°C, dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated to dryness under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 19-3. 1H NMR (400 MHz, DMSO-d6): S 5.12 (s, 1H), 4.32 (s, 2H), 0.87 (s, 9H), 0.08 (s, 6H). Preparation of compound 19-4 Under a nitrogen atmosphere, methanesulphonic anhydride (194 mg, 1.11 mmol) was slowly added to a solution of compound 19-3 (300 mg, 1.48 mmol) and triethylamine (0.6 mL, 4.45 mmol) in dichloromethane (3 mL). The reaction solution was stirred at 25°C for 2 hours. After the reaction was completed, the reaction was quenched with 20 mL of water, and the aqueous phase was extracted with dichloromethane (10 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain compound 19-4. 1H NMR (400 MHz, DMSO-d6) 5 = 4.40 (s, 2H), 3.23 (s, 3H), 0.87 (s, 10H), 0.09 (s, 6H). Preparation of compound 19-5 Under a nitrogen atmosphere, compound 19-4 (183 mg, 0.65 mmol) was added to a solution of compound 1-18 (100 mg, 0.22 mmol) and potassium carbonate (150 mg, 1.09 mmol) in N-N,dimethylformamide (2 mL). The reaction solution was stirred at 60°C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and diluted with 20 mL of water. The aqueous phase was extracted with ethyl acetate (10 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated to dryness under reduced pressure to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (0.1% FA / ACN, 80% to 90% over 10 min) to obtain compound 19-5. 1H NMR (400 MHz, CDCI3): 3 8.66 (s, 1H), 8.46 (d, J = 5.6 Hz, 1H), 8.16 (dd, J = 2.4, 5.6 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.88 - 7.81 (m, 1H), 7.16 - 7.10 (m, 1H), 7.03 - 6.91 (m, 1H), 5.58 (br s, 1H), 5.02 (d, J = 11.2 Hz, 1H), 4.21 (d, J = 1.6 Hz, 2H), 2.93 - 2.84 (m, 1H), 1.71 (s, 3H), 0.85 (s, 9H), 0.83 - 0.78 (m, 3H), 0.02 (s, 6H); m / z (ESI): [M+ H]+ =644.3. Preparation of example 19 Under a nitrogen atmosphere, a solution of compound 19-5 (60.0 mg, 0.09 mmol) in 3 mL of hydrogen chloride / methanol (2 M) was stirred at 25°C for 0.5 hours. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (column: Waters Xbridge 150 x 25 mm x 5 um; 30% to 60% over 10 min) to obtain example 19. 1H NMR (400 MHz, DMSO-d6): 3 10.72 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 2.4 Hz, 1H), 7.84 (dd, J = 2.4, 5.6 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.26 - 7.14 (m, 2H), 5.19 (t, J = 6.0 Hz, 1H), 5.11 (d, J = 10.4 Hz, 1H), 4.34 (dd, J = 7.6, 10.4 Hz, 1H), 4.06 (d, J = 4.0 Hz, 2H), 2.92 - 2.80 (m, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ =530.1. Example 20 Preparation of example 20 Under a nitrogen atmosphere, deuterium oxide (0.2 mL, 9.30 mmol) and potassium carbonate (15.42 mg, 0.11 mmol) were added to a solution of example 12 (50 mg, 0.09 mmol) in 1 mL of acetonitrile. The reaction solution was stirred at 24°C for 12 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was separated and purified by reversed-phase preparative chromatography (column: Phenomenex 150 x 25 mm x 10 um, Condition: water(FA)-CAN; Begin B:48, End B: 78, Gradient Time (min):11, 100%B Hold Time (min):4, FlowRate (ml / min): 2) to obtain example 20. 1H NMR (400 MHz, DMSO-d6): 8 10.71 (s, 1H), 8.49 (d, J = 5.4 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 2.4 Hz, 1H), 7.83 (dd, J = 2.4, 5.4 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.28 - 7.14 (m, 2H), 5.12 (d, J = 10.2 Hz, 1H), 4.33 (dd, J = 7.6, 10.2 Hz, 1H), 2.90 - 2.78 (m, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ = 501.1. Example 21 Preparation of compound 21-1 Under a nitrogen atmosphere, compound 1-15 (200 mg, 0.54 mmol) was added to methanol (2 mL), and the mixture was stirred at 25°C for 2 hours. The reaction solution was concentrated to dryness to obtain compound 21-1. m / z (ESI): [M+ H] + = 369.0. Preparation of compound 21-2 Under a nitrogen atmosphere, boron tribromide (2.04 g, 8.15 mmol) was added dropwise to a solution of compound 21-1 (2.00 g, 5.43 mmol) in dichloromethane (40 mL) at 0°C. The mixture was stirred at 25°C for 1.5 hours. Saturated aqueous sodium bicarbonate solution (20 mL) was slowly added dropwise to the reaction solution, and the mixture was extracted with dichloromethane (30 mL x 3). The combined organic phases were washed with saturated sodium chloride aqueous solution (20 mL x 2), dried over anhydrous sodium sulphate, filtered, and concentrated to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain compound 21-2. m / z (ESI): [M+ H] + = 355.1. Preparation of compound 21-3 Propargyl bromide (0.34 g, 2.82 mmol) was added to a suspension of compound 21-2 (1.00 g, 2.82 mmol) and potassium carbonate (1.95 g, 14.11) in DMF (10 mL). The mixture was stirred at 60°C for 2 hours. The reaction solution was filtered, and the filtrate was purified by reversed-phase column chromatography (0.1% formic acid system) to obtain compound 21-3. m / z (ESI): [M+ H] + = 393.1. Preparation of compound 21-4 Lithium hydroxide (497.33 mg, 11.85 mmol) was added to a solution of compound 21-3 (930 mg, 2.37 mmol) in THF (12 mL), methanol (4 mL), and water (4 mL). The mixture was stirred at 25°C for 1 hour. The reaction solution was diluted with water (30 mL), adjusted to pH 4 with dilute hydrochloric acid (1 mol / L), and extracted with dichloromethane (30 mL x 3). The combined organic phases were washed with saturated sodium chloride aqueous solution (20 mL x 2), dried over anhydrous sodium sulphate, filtered, and concentrated to obtain compound 21-4. m / z (ESI): [M-H] - = 377.0. Preparation of compound 21-5 To a solution of compound 21-4 (70 mg, 0.19 mmol) in DCM (2 mL) were added DMF (2.9 pL, 0.04 mmol) and oxalyl chloride (31.8 pL, 0.37 mmol). The mixture was stirred at 25°C for 1 hour. The mixture was concentrated to obtain compound 21-5. Preparation of compound 21-6 Preparation of compound 21-8 Under a nitrogen atmosphere, di-tert-butyl dicarbonate (2.8 mL, 13.1 mmol) and triethylamine (1.8 mL, 13.1 mmol) were added to a solution of compound 21-7 (1.00 g, 6.57 mmol) and 4-dimethylaminopyridine (0.40 g, 3.29 mmol) in 10 mL of dichloromethane. The reaction solution was stirred at 26°C for 16 hours. Additional di-tert-butyl dicarbonate (2.8 mL, 13.1 mmol) was added, and the reaction solution was warmed to 40°C and stirred for another 16 hours. After the reaction was completed, the mixture was diluted with 200 mL of water, and subjected to liquid separation. The aqueous phase was extracted with ethyl acetate (100 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - 5 / 1) to obtain compound 21-8. 1H NMR (400 MHz, CDCI3): S 8.57 (d, J = 5.6 Hz, 1H), 8.03 (d, J = 2.4 Hz, 1H), 7.71 (dd, J = 2.0, 5.6 Hz, 1H), 7.00 (s, 1H), 4.00 (s, 3H), 1.54 (s, 9H); m / z (ESI): [M+ H]+ =253.0. Preparation of compound 21-9 At 0°C, m-chloroperoxybenzoic acid (965.69 mg, 4.76 mmol, 85% content) was slowly added portionwise to a solution of compound 21-8 (600 mg, 2.38 mmol) in 10 mL of dichloromethane. The reaction solution was warmed to 26°C and stirred for 16 hours. After the reaction was completed, the reaction solution was filtered. The reaction was quenched by slow dropwise addition of the filtrate to 50 mL of saturated aqueous sodium sulphite solution. After a negative result with starch-potassium iodide test paper was obtained, the aqueous phase was extracted with dichloromethane (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 to 100% methanol elution) to obtain compound 21-9. 1H NMR (400 MHz,CDCl3): J 8.13 ( d, J = 7.2 Hz, 1H), 7.86 (s, 1H), 7.53 (d, J = 4.8 Hz, 1H), 3.96 (s, 3H), 1.51 (s, 9H); m / z (ESI): [M+ H]+ =269.0. Preparation of compound 21-6 Under a nitrogen atmosphere, trifluoroacetic acid (2.00 mL, 26.9 mmol) was slowly added dropwise to a solution of compound 21-9 (170 mg, 0.63 mmol) in 2 mL of dichloromethane. The mixed solution was stirred at 25°C for 2 hours and then concentrated. The residue was adjusted to pH 10 with triethylamine and purified by reversed-phase preparative chromatography (0.1% FA / ACN, 100% water over 3 min) to obtain compound 21-6. Preparation of compound 21-10 Under a nitrogen atmosphere, compound 21-5 (70.0 mg, 0.18 mmol) was added to a solution of compound 21-6 (148 mg, 0.88 mmol) and triethylamine (0.1 mL, 0.88 mmol) in 0.5 mL of dichloromethane. The reaction solution was stirred at 25°C for 1.5 hours. After the reaction was completed, the reaction solution was quenched with 20 mL of water, and the aqueous phase was extracted with dichloromethane (10 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (0.1% FA / ACN, 50% to 60% over 5 min) to obtain compound 21-10. m / z (ESI): [M+ H]+ =529.2. Preparation of example 21 Under a nitrogen atmosphere, compound 21-10 (70.0 mg, 0.13 mmol) was added to 10 mL of ammonia in methanol (7 M). The reaction solution was stirred at 25°C for 16 hours, and then concentrated to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (column: Waters Xbridge 150 x 25 mm x 5 um, 32% to 62% over 11 min) to obtain example 21. 1H NMR (400 MHz, DMSO-d6): J = 10.78 (s, 1H), 10.59 (d, J = 4.4 Hz, 1H), 8.52 (d, J = 3.2 Hz, 1H), 8.31 (d, J = 7.2 Hz, 1H), 8.23 (d, J = 4.4 Hz, 1H), 7.88 (dd, J = 3.2, 7.2 Hz, 1H), 7.26 - 7.16 (m, 2H), 5.10 (d, J = 10.4 Hz, 1H), 4.98 - 4.85 (m, 2H), 4.32 (dd, J = 7.6, 10.4 Hz, 1H), 3.63 (t, J = 2.4 Hz, 1H), 2.88 - 2.66 (m, 1H), 1.62 (s, 3H), 0.73 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ =514.1. Examples 22 and 23 Preparation of compound 22-2 Under a nitrogen atmosphere, caesium carbonate (20.55 g, 63.08 mmol) and [1,1-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane (1.29 g, 1.58 mmol) were added to a solution of compound 22-1 (5 g, 31.54 mmol) and potassium vinyltrifluoroborate (5.07 g, 37.85 mmol) in a mixture of 150 mL of 2-methyltetrahydrofuran and 15 mL of water. The reaction solution was warmed to 90°C and stirred for 4 hours. After the reaction was completed, the reaction solution was cooled to room temperature and concentrated. The residue was diluted with 50 mL of water, and the mixture was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified sequentially by reversed-phase preparative chromatography (0.1% FA system) and silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1 to 2 / 1) to obtain compound 22-2. 1H NMR (400 MHz, CDCI3): 3 9.39 (d, J = 2.4 Hz, 1H), 8.44 (dd, J = 2.4, 8.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 6.91 (dd, J = 10.8, 17.6 Hz, 1H), 6.46 (d, J = 17.6 Hz, 1H), 5.75 (d, J = 10.8 Hz, 1H). Preparation of compound 22-3 Under a nitrogen atmosphere, a solution of osmium tetroxide (63.55 mg, 0.25 mmol) in water (4.3 mL) was slowly added dropwise to a solution of N-methylmorpholine oxide (4353.92 mg, 37.17 mmol) and compound 22-2 (1860.00 mg, 12.39 mmol) in a mixture of 4.3 mL of water and 16 mL of acetone. After the dropwise addition was completed, the reaction solution was stirred at 25°C for another 3 hours. After the reaction was completed, the reaction solution was cooled to 0°C, quenched with 50 mL of saturated aqueous sodium sulphite solution, and stirred for 15 minutes. The aqueous phase was extracted with ethyl acetate (50 mL x 15), and the combined organic layers were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1 to 0 / 1) to obtain compound 22-3. 1H NMR (400 MHz, DMSO-d6): 3 9.29 (d, J = 2.4 Hz, 1H), 8.58 (dd, J = 2.8, 8.8 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 5.76 (d, J = 5.2 Hz, 1H), 4.79 (t, J = 6.0 Hz, 1H), 4.72 (q, J = 5.2 Hz, 1H), 3.78 - 3.69 (m, 1H), 3.62 - 3.53 (m, 1H). Preparation of compound 22-4 Under a nitrogen atmosphere, p-toluenesulphonic acid (120 mg, 0.67 mmol) and 2,2-dimethoxypropane (2.1 mL, 16.70 mmol) were added to a solution of compound 22-3 (1230.00 mg, 6.68 mmol) in a mixture of 20 mL of 2-methyltetrahydrofuran and 20 mL of acetone. The reaction solution was stirred at 25°C for 16 hours. After the reaction was completed, the reaction solution was quenched with 10 mL of saturated aqueous sodium bicarbonate solution, and diluted with 50 mL of water. The aqueous phase was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain compound 22-4. 1H NMR (400 MHz, DMSO-d6): S 9.32 (d, J = 2.4 Hz, 1H), 8.63 (dd, J = 2.4, 8.4 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 5.27 (t, J = 6.4 Hz, 1H), 4.45 (dd, J = 7.2, 8.4 Hz, 1H), 3.91 (dd, J = 6.0, 8.4 Hz, 1H), 1.46 (s, 3H), 1.43 (s, 3H); m / z (ESI): [M+ H]+ = 224.9. Preparation of compound 22-5 Under an argon atmosphere, 10% palladium on carbon catalyst (wet, 100 mg) was added to a solution of compound 22-4 (700 mg, 3.12 mmol) in 28 mL of ethyl acetate. The reaction solution was purged three times with hydrogen, and then stirred under a hydrogen atmosphere (15 psi) at 25°C for 6 hours. After the reaction was completed, the reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure to obtain compound 22-5. Preparation of compound 22-6 Under a nitrogen atmosphere, triethylamine (559.4 pL, 4.02 mmol) was added to a solution of compound 1-15 (500 mg, 1.34 mmol) and compound 22-5 (260.56 mg, 1.34 mmol) in 10 mL of dichloromethane. The reaction solution was reacted at 25°C for 1 hour. After the reaction was completed, the reaction solution was diluted with 10 mL of water, and the aqueous phase was extracted with dichloromethane (15 mL x 3). The combined organic phases were washed with 30 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1 to 2 / 1) to obtain compound 22-6. 1H NMR (400 MHz, DMSO-d6): S 10.44 (s, 1H), 8.70 (dd, J = 2.4, 5.2 Hz, 1H), 8.05 (ddd, J = 2.4, 5.2, 8.4 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.22 - 7.10 (m, 2H), 5.17 - 4.99 (m, 2H), 4.32 (dd, J = 6.8, 8.0 Hz, 1H), 4.23 (dd, J = 7.6, 10.4 Hz, 1H), 3.94 (d, J = 2.0 Hz, 3H), 3.81 (dd, J = 6.8, 8.0 Hz, 1H), 2.79 - 2.72 (m, 1H), 1.60 (s, 3H), 1.41 (s, 3H), 1.38 (s, 3H), 0.73 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ = 531.2. Preparation of compound 22-7 Under a nitrogen atmosphere, boron tribromide (0.8 mL, 1.67 mmol) was slowly added to a solution of compound 22-6 (590 mg, 1.11 mmol) in 12 mL of dichloromethane at 0°C. The reaction solution was warmed to 25°C and stirred for 1.5 hours. After the reaction was completed, the reaction was quenched with 10 mL of saturated sodium bicarbonate solution, and the aqueous phase was extracted with dichloromethane (20 mL x 3). The combined organic phases were washed with 40 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) and reversed-phase column chromatography (0.1% formic acid system) to obtain compound 22-7. 1H NMR (400 MHz, DMSO-d6): 3 10.49 (br s, 1H), 8.66 (dd, J = 2.4, 9.2 Hz, 1H), 8.35 (s, 1H), 7.99 (dt, J = 2.4, 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.01 (t, J = 6.8 Hz, 1H), 6.80 (q, J = 8.8 Hz, 1H), 5.57 - 5.20 (m, 1H), 5.10 (d, J = 10.4 Hz, 1H), 4.89 - 4.59 (m, 1H), 4.53 (dd, J = 4.4, 6.8 Hz, 1H), 4.22 (dd, J = 7.6, 10.0 Hz, 1H), 3.62 (dd, J = 4.0, 10.8 Hz, 2H), 2.83 (t, J = 7.2 Hz, 1H), 1.58 (s, 3H), 0.70 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H]+ = 477.2. Preparation of examples 22 and 23 Under a nitrogen atmosphere, bromopropyne (32.6 pL, 0.38 mmol) was slowly added to a solution of compound 22-7 (90 mg, 0.19 mmol) and potassium carbonate (130.54 mg, 0.94 mmol) in 1.5 mL of N-N,dimethylformamide. The reaction solution was warmed to 60°C and stirred for 2 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The filtrate was purified by reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x 5 um; mobile phase: water (NH4HCO3), ACN; B%: 40% - 60%, 25 min) to obtain a mixture of example 22 and example 23. The mixture was separated by SFC (Column: DAICEL CHIRALCEL OX (250 mm x 30 mm x 10 um); Condition: CO2-EtOH (0.1% NH3H2O); B%: 15-15; Gradient Time (min): 6.2; 100% B Hold Time (min): 0; FlowRate (ml / min): 150) to obtain two single isomers. Example 22 (retention time=1.505 minutes): 1H NMR (400 MHz, DMSO-d6): 3 10.36 (s, 1H), 8.63 (d, J = 2.4 Hz, 1H), 7.99 (dd, J = 2.4, 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.27 - 7.15 (m, 2H), 5.33 (d, J = 4.4 Hz, 1H), 5.10 (d, J = 10.4 Hz, 1H), 4.92 (dd, J = 2.4, 4.0 Hz, 2H), 4.64 (t, J = 5.6 Hz, 1H), 4.53 (td, J = 4.4, 6.8 Hz, 1H), 4.31 (dd, J = 7.6, 10.4 Hz, 1H), 3.66 (t, J = 2.4 Hz, 1H), 3.62 (ddd, J = 4.4, 6.0, 10.8 Hz, 1H), 3.43 (td, J = 6.4, 11.2 Hz, 1H), 2.83 (t, J = 7.6 Hz, 1H), 1.60 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H]+ = 515.3. Example 23 (retention time=1.649 minutes): 1H NMR (400 MHz, DMSO-d6) 5 = 10.35 (s, 1H), 8.66 (d, J = 2.4 Hz, 1H), 7.97 (dd, J = 2.4, 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.26 - 7.15 (m, 2H), 5.33 (d, J = 4.8 Hz, 1H), 5.10 (d, J = 10.4 Hz, 1H), 4.97 - 4.86 (m, 2H), 4.64 (t, J = 5.6 Hz, 1H), 4.53 (td, J = 4.4, 6.8 Hz, 1H), 4.31 (dd, J = 7.6, 10.4 Hz, 1H), 3.66 (t, J = 2.4 Hz, 1H), 3.62 (ddd, J = 4.4, 6.4, 10.7 Hz, 1H), 3.43 (td, J = 6.4, 10.8 Hz, 1H), 2.89 - 2.77 (m, 1H), 1.61 (s, 3H), 0.74 (d, J = 5.8 Hz, 3H); m / z (ESI): [M + H]+ = 515.2. Examples 24 and 25 24-1                                  24-2 Example 24 Example 25 Preparation of compound 24-1 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (7.15 g, 29.64 mmol) was added to a solution of compound 21-2 (2.10 g, 5.93 mmol) and compound 12-2 (3.86 g, 29.64 mmol) in 80 mL of dioxane. The reaction solution was warmed to 40°C and stirred for 16 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and quenched with 100 mL of water. The aqueous phase was extracted with ethyl acetate (50 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 50 / 1 - 30 / 1) to obtain compound 24-1. 1H NMR (400 MHz, CDCI3): 3 6.98 - 6.92 (m, 1H), 6.92 - 6.86 (m, 1H), 4.92 (d, J = 10.4 Hz, 1H), 4.28 - 4.19 (m, 1H), 3.71 (s, 3H), 2.91 - 2.69 (m, 1H), 1.65 (s, 3H), 0.81 - 0.74 (m, 3H), 0.15 (s, 9H). Preparation of compound 24-2 Under a nitrogen atmosphere, a solution of lithium hydroxide (1.01 g, 24.1 mmol) in water (8 mL) was added dropwise to a solution of compound 24-1 (2.25 g, 4.82 mmol) in 24 mL of tetrahydrofuran and 8 mL of methanol. The reaction solution was stirred at 26°C for 1 hour. After the reaction was completed, the mixture was concentrated under reduced pressure to remove the low-boiling solvents. The residue was adjusted to pH 5 with 2 M dilute hydrochloric acid, and the aqueous phase was extracted with ethyl acetate (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 to ethyl acetate / methanol = 5 / 1) to obtain compound 24-2. 1H NMR (400 MHz, DMSO-d6): § 7.24 - 7.08 (m, 2H), 4.76 (d, J = 10.4 Hz, 1H), 4.16 - 4.05 (m, 1H), 3.64 (s, 1H), 2.74 - 2.66 (m, 1H), 1.51 (s, 3H), 0.67 (d, J = 6.0 Hz, 3H); m / z (ESI): [M- H]- =379.1. Preparation of compound 24-3 Under a nitrogen atmosphere, oxalyl chloride (67.7 pL, 0.79 mmol) was slowly added dropwise to a solution of compound 24-2 (100 mg, 0.26 mmol) and N,N-dimethylformamide (2.0 pL, 0.03 mmol) in 2 mL of dichloromethane. The reaction solution was reacted at 26°C for 2 hours. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain compound 24-3. Preparation of compound 24-5 Under a nitrogen atmosphere, a solution of compound 24-3 (100 mg, 0.25 mmol) in 1 mL of dichloromethane was added dropwise to a solution of compound 24-4 (70.3 mg, 0.5 mmol) and triethylamine (0.1 mL, 0.75 mmol) in 1 mL of dichloromethane. The reaction solution was stirred at 26°C for 1 hour. After the reaction was completed, the mixture was diluted with 50 mL of water, and the aqueous phase was extracted with dichloromethane (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - 5 / 1) to obtain compound 24-5. 1H NMR (400 MHz, CDCI3): 3 8.39 - 8.28 (m, 2H), 7.52 (d, J = 2.0 Hz, 1H), 7.16 - 7.11 (m, 1H), 7.09 (dd, J = 2.0, 5.6 Hz, 1H), 7.03 - 6.95 (m, 1H), 4.99 (d, J = 11.2 Hz, 1H), 4.20 (s, 1H), 2.88 - 2.76 (m, 1H), 2.54 (s, 3H), 2.37 (s, 1H), 1.70 (s, 3H), 0.84 - 0.76 (m, 3H); m / z (ESI): [M+ H]+ = 503.2. Preparation of examples 24 and 25 Under a nitrogen atmosphere, iodobenzene diacetate (216.7 mg, 0.67 mmol) was added to a solution of compound 24-5 (160 mg, 0.32 mmol) and ammonium acetate (39.27 mg, 0.51 mmol) in 4 mL of methanol. The reaction solution was stirred at 26°C for 1 hour. After the reaction was completed, the mixture was diluted with 20 mL of water, and concentrated under reduced pressure to remove the low-boiling solvents. The aqueous phase was extracted with ethyl acetate (10 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (0.1% NH4OH, 40% to 50% over 10 min), and then resolved by SFC (column: DAICEL CHIRALPAK AD (250 mmx30 mm,10 gm), CO2-EtOH (0.1% Nft^O), 25% over 4.1 min, flow rate: 60 mL / min) to obtain two single isomers. Example 24 (retention time=1.265 minutes): 1H NMR (400 MHz, DMSO-d6): 3 10.87 (s, 1H), 8.57 (d, J = 5.6 Hz, 1H), 8.35 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 2.0, 5.6 Hz, 1H), 7.30 - 7.13 (m, 2H), 5.13 (d, J = 10.4 Hz, 1H), 4.39 - 4.27 (m, 2H), 3.63 (s, 1H), 3.11 (s, 3H), 2.89 - 2.78 (m, 1H), 1.61 (s, 3H), 0.74 (d, J = 6.4 Hz, 3H); m / z (ESI): [M+ H]+ =534.1. Example 25 (retention time=1.412 minutes): 1H NMR (400 MHz, DMSO-d6): 3 10.87 (s, 1H), 8.57 (d, J = 5.6 Hz, 1H), 8.35 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 2.0, 5.6 Hz, 1H), 7.29 - 7.14 (m, 2H), 5.13 (d, J = 10.4 Hz, 1H), 4.39 - 4.28 (m, 2H), 3.63 (s, 1H), 3.11 (d, J = 1.2 Hz, 3H), 2.90 - 2.78 (m, 1H), 1.61 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ =534.1. Example 26 26-3 Preparation of compound 26-2 Under a nitrogen atmosphere, compound 26-1 (380 mg, 2.55 mmol) was added to 10 mL of ammonia solution in methanol (6 M). The reaction solution was stirred at 25°C for 20 hours. The reaction solution was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate =    1 / 1    -    1 / 1, dichloromethane / methanol = 20 / 1 - 10 / 1) to obtain compound 26-2. 1H NMR (400 MHz, DMSO-d6): S 7.83 (brs, 1H), 7.32 (brs, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.73 (d, J = 2.4 Hz, 1H), 6.58 (dd, J = 2.4, 8.0 Hz, 1H), 5.16 (s, 2H), 5.07 (t, J = 5.6 Hz, 1H), 4.36 (d, J = 5.6 Hz, 2H). Preparation of compound 26-3 Under a nitrogen atmosphere, imidazole (40.97 mg, 0.60 mmol) and tert-butyl dimethylsilyl chloride (68.02 mg, 0.45 mmol) were added to a solution of compound 26-2 (50.0 mg, 0.30 mmol) in 1 mL of N,N-dimethylformamide. The reaction solution was reacted at 25°C for 12 hours. After the reaction was completed, the reaction solution was quenched with 20 mL of water. The aqueous phase was extracted with ethyl acetate (20 mL x 2). The combined organic phases were washed with 20 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1-0 / 1) to obtain compound 26-3. 1H NMR (400 MHz, DMSO-d6): S 7.61 (brs, 1H), 7.21 (brs, 1H), 7.09 (d, J = 8.0 Hz, 1H), 6.67 (d, J = 2.4 Hz, 1H), 6.58 (dd, J = 2.4, 8.0 Hz, 1H), 5.14 (s, 2H), 4.65 (s, 2H), 0.86 (s, 9H), 0.04 (s, 6H). Preparation of compound 26-4 Under a nitrogen atmosphere, compound 26-3 (53.97 mg, 0.19 mmol) and triethylamine (87.1 uL, 0.63 mmol) were added to a solution of compound 24-3 (50.0 mg, 0.13 mmol) in 2 mL of dichloromethane. The reaction solution was reacted at 25°C for 1 hour. After the reaction was completed, the reaction solution was quenched with 20 mL of water. The aqueous phase was extracted with dichloromethane (20 mL x 2). The combined organic phases were washed with 20 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1-1 / 1) to obtain compound 26-4. 1H NMR (400 MHz, CDCh): 3 8.47 (s, 1H), 8.03 - 7.93 (m, 2H), 7.75 (d, J = 2.4 Hz, 1H), 7.29 (s, 1H), 7.20 - 7.15 (m, 1H), 7.02 - 6.94 (m, 1H), 5.68 (brs, 1H), 5.00 (d, J = 11.2 Hz, 1H), 4.78 (s, 2H), 4.25 (dd, J = 7.6, 11.2 Hz, 1H), 2.88 - 2.75 (m, 1H), 2.38 (s, 1H), 1.71 (s, 3H), 0.88 (s, 9H), 0.83 - 0.78 (m, 3H), 0.10 (s, 6H); m / z (ESI): [M + H]+ = 643.3. Preparation of example 26 Under a nitrogen atmosphere, a solution of tetrabutylammonium fluoride in tetrahydrofuran (133.4 gL, 0.13 mmol, 1 M) was added to a solution of compound 26-4 (60.0 mg, 0.09 mmol) in 1 mL of tetrahydrofuran. The reaction solution was reacted at 25°C for 0.5 hours. After the reaction was completed, the mixture was concentrated to obtain a crude product, which was purified by reversed-phase preparative chromatography (Phenomenex luna C18 150 x 25 mm x 10 um; mobile phase: water(FA)-ACN; B%: 45% - 75%, 25 min), followed by a second reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x 5 um; mobile phase: water(NH4HCO3), ACN; B%: 42% - 72%, 25 min) to obtain example 26. 1H NMR (400 MHz, DMSO-d6): 3 10.29 (s, 1H), 7.86 (brs, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.65 (dd, J = 2.0, 8.0 Hz, 1H), 7.48 - 7.37 (m, 2H), 7.27 - 7.12 (m, 2H), 5.24 (brs, 1H), 5.07 (d, J = 10.4 Hz, 1H), 4.53 (d, J = 3.6 Hz, 2H), 4.32 (dd, J = 7.6, 10.4 Hz, 1H), 3.64 (s, 1H), 2.83 (t, J = 7.2 Hz, 1H), 1.60 (s, 3H), 0.73 (d, J = 6.0 Hz, 3H); m / z (ESI): [M -17]+ = 511.1. Example 27 24 3                              271                             Example 27 Preparation of compound 27-1 Under a nitrogen atmosphere, triethylamine (365.5 pL, 2.63 mmol) was added to a solution of compound 24-3 (103.67 mg, 0.26 mmol) in dichloromethane (1 mL), followed by the dropwise addition of a solution of methyl 4-aminopyridine-2-carboxylate (80.01 mg, 0.53 mmol) in dichloromethane (0.5 mL). The reaction solution was stirred at 26°C for 2 hours. After the reaction was completed, the mixture was diluted with 30 mL of water. The aqueous phase was extracted with dichloromethane (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 1) to obtain compound 27-1. 1H NMR (400 MHz, CDCh): 3 8.63 (d, J = 5.6 Hz, 1H), 8.58 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.93 (dd, J = 5.6, 2.0 Hz, 1H), 7.05 - 7.19 (m, 1H), 6.93 - 7.05 (m, 1H), 5.03 (d, J = 11.2 Hz, 1H), 4.21 - 4.32 (m, 1H), 4.01 (s, 3H), 2.73 - 2.94 (m, 1H), 2.38 (s, 1H), 1.72 (s, 3H), 0.76 - 0.87 (m, 3H); m / z (ESI): [M - H]- = 513.2. Preparation of example 27 Under a nitrogen atmosphere, potassium cyanide (2 mg, 0.03 mmol) and aqueous hydroxylamine solution (0.5 mL, 8.16 mmol, 50% in water) were sequentially added to a solution of compound 27-1 (30 mg, 0.06 mmol) in a mixture of 0.5 mL of methanol and 0.5 mL of tetrahydrofuran. The reaction solution was stirred at 26°C for 12 hours. After the reaction was completed, the reaction solution was poured into 20 mL of saturated aqueous sodium bicarbonate solution to quench the reaction, and the mixture was extracted with dichloromethane (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (Column Phenomenex luna C18 150*25 mm* 10 um; mobile phase: water(TFA)-ACN; B%: 28% - 58%, 14 min) to obtain example 27. 1H NMR (400 MHz, DMSO-d6): S 11.38 (s, 1H), 10.70 (s, 1H), 8.45 (d, J = 5.6 Hz, 1H), 8.22 (d, J = 2.0 Hz, 1H), 7.81 (dd, J = 5.6, 2.0 Hz, 1H), 7.07 - 7.38 (m, 2H), 5.11 (d, J = 10.4 Hz, 1H). 4.10 - 4.45 (m, 1H), 3.63 (s, 2H), 2.84 (s, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H]+ = 516.1. Example 28 24 3                               28'1                                  Example 28 Preparation of compound 28-1 Under a nitrogen atmosphere, triethylamine (348.6 ^L, 2.51 mmol) and 4-aminopyridine-2-carbonitrile (59.75 mg, 0.50 mmol) were sequentially added to a solution of compound 24-3 (100 mg, 0.25 mmol) in 1 mL of dichloromethane. The reaction solution was stirred at 26°C for 2 hours. After the reaction was completed, the mixture was diluted with 10 mL of water and extracted with dichloromethane (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated to obtain a crude product, which was purified by preparative silica gel thin-layer chromatography (petroleum ether / ethyl acetate = 1 / 1) to obtain compound 28-1. 1H NMR (400 MHz, CDCl3): S 8.67 - 8.53 (m, 2H), 8.08 - 7.99 (m, 1H), 7.70 - 7.60 (m, 1H), 7.16 - 7.07 (m, 1H), 7.06 - 6.91 (m, 1H), 5.13 - 4.94 (m, 1H), 4.31 - 4.18 (m, 1H), 2.91 - 2.78 (m, 1H), 2.44 - 2.36 (m, 1H), 1.75 - 1.67 (m, 3H), 0.86 - 0.76 (m, 3H); m / z (ESI): [M + H]+ = 482.1. Preparation of example 28 Under a nitrogen atmosphere, hydroxylamine hydrochloride (7.69 mg, 0.11 mmol) and sodium carbonate (23.47 mg, 0.22 mmol) were sequentially added to a solution of compound 28-1 (41 mg, 0.09 mmol) in 2 mL of ethanol. The reaction solution was stirred at 25°C for 1 hour. After the reaction was completed, the mixture was filtered, and the filtrate was adjusted to pH 5 with 2 N hydrochloric acid. The mixture was purified by reversed-phase preparative chromatography (Column Phenomenex luna C18 150*25 mm* 10 um Condition water(FA)-CAN Begin B 43 End B 73 Gradient Time (min) 11 100%B Hold Time (min) 4 FlowRate (ml / min) 25) to obtain example 28. 1H NMR (400 MHz, DMSO-d6): 3 10.74 - 10.50 (m, 1H), 9.93 - 9.75 (m, 1H), 8.47 - 8.37 (m, 1H), 8.22 - 8.08 (m, 1H), 7.69 - 7.56 (m, 1H), 7.32 - 7.06 (m, 2H), 5.93 - 5.65 (m, 2H), 5.22 - 4.91 (m, 1H), 4.48 - 4.15 (m, 1H), 3.67 - 3.58 (m, 1H), 2.89 - 2.78 (m, 1H), 1.70 - 1.53 (m, 3H), 0.87 - 0.59 (m, 3H); m / z (ESI): [M + H]+ = 515.2. Example 29 Example 29 Preparation of example 29 Under a nitrogen atmosphere, triethylamine (139.4 pL, 1.00 mmol) was added to a solution of compound 24-3 (100 mg, 0.25 mmol) in 0.5 mL of dichloromethane, followed by the addition of 4-aminopyridine-2-sulphonamide (45.17 mg, 0.26 mmol). The mixture was stirred at 26°C for 2 hours. After the reaction was completed, the reaction solution was quenched with 20 mL of water-, and extracted with dichloromethane (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (Column Waters Xbridge 150*25 mm* 5 um; mobile phase: water(NH3H2O)-ACN; B%: 38% - 68%, 12 min) to obtain example 29. 1H NMR (400 MHz, DMSO-d6): 3 10.52 (s, 1H), 8.09 - 8.31 (m, 1H), 7.75 (dt, J = 7.6, 2.0 Hz, 1H), 7.44 - 7.61 (m, 2H), 7.36 (s, 2H), 7.08 - 7.28 (m, 2H), 5.10 (d, J = 10.4 Hz, 1H), 4.34 (dd, J = 10.32, 7.44 Hz, 1H), 3.64 (s, 1H), 2.85 (s, 1H), 1.62 (s, 3H), 0.63 - 0.83 (m, 3H); m / z (ESI): [M + H]+ = 535.2. Examples 30 and 31 Example 31 Preparation of compound 30-1 Under a nitrogen atmosphere, a solution of compound 24-3 (300 mg, 0.75 mmol) in 2 mL of dichloromethane was added dropwise to a solution of 3-(methylthio)aniline (35.16 mg, 0.25 mmol) and triethylamine (0.3 mL, 2.26 mmol) in 2 mL of dichloromethane. The reaction solution was stirred at 26°C for 2 hours. After the reaction was completed, the mixture was diluted with 50 mL of water, and the aqueous phase was extracted with dichloromethane (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1 - 5 / 1) to obtain compound 30-1. 1H NMR (400 MHz, CDCI3): J 8.30 (s, 1H), 7.57 - 7.51 (m, 1H), 7.26 - 7.20 (m, 2H), 7.20 - 7.14 (m, 1H), 7.03 - 6.94 (m, 2H), 5.00 (d, J = 11.2 Hz, 1H), 4.28 (dd, J = 7.6, 11.2 Hz, 1H), 2.88 - 2.76 (m, 1H), 2.47 (s, 3H), 2.37 (s, 1H), 1.70 (s, 3H), 0.84 - 0.76 (m, 3H); m / z (ESI): [M+ H]+ =502.1. Preparation of examples 30 and 31 Under a nitrogen atmosphere, iodobenzene diacetate (407 mg, 1.26 mmol) was added to a solution of compound 30-1 (300 mg, 0.60 mmol) and ammonium acetate (73.8 mg, 0.96 mmol) in 5 mL of methanol. The reaction solution was stirred at 26°C for 1 hour. After the reaction was completed, the mixture was concentrated under reduced pressure to remove the low-boiling solvents to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 1 - 0 / 1) and reversed-phase preparative chromatography (0.1% FA / ACN, 50% to 60% over 5 min) to obtain a mixture of example 30 and example 31. The mixture was resolved by SFC (column: DAICEL CHIRALPAK AD (250 mm x 30 mm, 10 um), CO2-EtOH (0.1% NH3H2O), 30% to 30% over 2.7 min, 60 mL / min) to obtain two single isomers. Example 30 (retention time=0.915 minutes): 1H NMR (400 MHz, DMSO-d6): 8 10.53 (s, 1H), 8.24 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 - 7.49 (m, 1H), 7.27 - 7.14 (m, 2H), 5.09 (d, J = 10.4 Hz, 1H), 4.33 (dd, J = 7.6, 10.4 Hz, 1H), 4.22 - 4.15 (m, 1H), 3.64 (s, 1H), 3.02 (s, 3H), 2.92 - 2.77 (m, 1H), 1.61 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ =533.3. Example 31 (retention time=1.165 minutes): 1H NMR (400 MHz, DMSO-d6): 8 10.54 (s, 1H), 8.24 (t, J = 1.8 Hz, 1H), 7.88 - 7.82 (m, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 - 7.49 (m, 1H), 7.30 - 7.11 (m, 2H), 5.09 (d, J = 10.4 Hz, 1H), 4.33 (dd, J = 7.6, 10.4 Hz, 1H), 4.19 (s, 1H), 3.64 (s, 1H), 3.02 (d, J = 0.8 Hz, 3H), 2.90 - 2.77 (m, 1H), 1.61 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ =533.2. Example 32 Preparation of compound 32-2 Under a nitrogen atmosphere, tert-butyl dimethylsilyl chloride (865 mg, 5.74 mmol) was added to a solution of compound 32-1 (300 mg, 2.87 mmol) and imidazole (586 mg, 8.61 mmol) in 5 mL of N,N-dimethylformamide. The reaction solution was reacted at 20°C for 3 hours. After the reaction was completed, the reaction solution was quenched with 50 mL of water and extracted with ethyl acetate (25 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified by column chromatography (eluting with petroleum ether) to obtain compound 32-2. 1H NMR (400 MHz, CDCl3): 8 4.37 (t, J = 2.0 Hz, 2H), 4.18 (t, J = 2.0 Hz, 2H), 0.92 (s, 9H), 0.13 (s, 6H). Preparation of compound 32-3 Under a nitrogen atmosphere, a solution of compound 32-2 (28.6 mg, 0.13 mmol) in N,N-dimethylformamide (1 mL) was slowly added to a solution of compound 1-18 (60 mg, 0.13 mmol) and potassium carbonate (90.3 mg, 0.65 mmol) in 1 mL of N,N-dimethylformamide. The reaction solution was warmed to 60°C and stirred for 2 hours. After the reaction was completed, the reaction solution was cooled and then filtered. The filtrate was separated by reversed-phase preparative chromatography to obtain compound 32-3. Preparation of example 32 Compound 32-3 (25 mg, 0.04 mmol) was dissolved in a solution of hydrogen chloride in methanol (2 mL, 2 M), and the mixture was stirred at 25°C for 0.5 hours. After the reaction was completed, the mixture was concentrated, diluted with 2 mL of methanol, and adjusted to pH=8 with aqueous ammonia. The mixture was separated and purified by reversed-phase preparative chromatography (column: Waters Xbridge 150 x 25 mm x 5 um, water (NH4HCO3)-ACN, 38%-68% over 9 min) to obtain example 32. 1H NMR (400 MHz, DMSO-d6): S 10.73 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.63 (d, J = 1.6 Hz, 1H), 7.28 - 7.14 (m, 2H), 5.21 (t, J = 6.0 Hz, 1H), 5.11 (d, J = 10.4 Hz, 1H), 4.94 (d, J = 1.6 Hz, 2H), 4.34 (dd, J = 7.6, 10.4 Hz, 1H), 4.10 - 4.03 (m, 2H), 2.91 - 2.79 (m, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.4 Hz, 3H); m / z (ESI): [M+ H]+ = 528.2. Example 33 Preparation of example 33 Under a nitrogen atmosphere, [1,1-bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane (13.81 mg, 0.02 mmol), cuprous iodide (6.48 mg, 0.03 mmol), triethylamine (117.5 pL, 0.85 mmol), and compound 33-1 (142.23 mg, 1.69 mmol) were added to a solution of compound 3-1 (100 mg, 0.17 mmol) in 2 mL of N,N-dimethylformamide. The reaction solution was stirred at 100°C for 16 hours. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 40 mL of water and extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was purified and separated by reversed-phase preparative chromatography (Column: Waters Xbridge 150 x 25 mm x 5 um; Condition: water (NH4HCO3)-ACN; Begin B:38, End B:68; Gradient Time (min): 10; 100%B Hold Time (min):4, Flow Rate (ml / min): 25) to obtain example 33. 1H NMR (400 MHz, DMSO-d6): § 10.75 (s, 1H), 8.49 (d, J = 5.4 Hz, 1H), 8.29 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 1.6 Hz, 1H), 7.84 (dd, J = 2.0, 5.4 Hz, 1H), 7.62 (d, J = 1.6 Hz, 1H), 7.53 - 7.45 (m, 1H), 7.28 (dd, J = 4.0, 8.8 Hz, 1H), 5.69 (s, 1H), 5.22 (d, J = 10.2 Hz, 1H), 4.36 (dd, J = 7.6, 10.2 Hz, 1H), 2.96 (t, J = 7.6 Hz, 1H), 1.64 (s, 3H), 1.51 (s, 6H), 0.75 - 0.68 (m, 3H); m / z (ESI): [M - 17] + = 508.2. Example 34 Preparation of compound 34-2 Under a nitrogen atmosphere, benzoyl chloride (322.7 pL, 2.78 mmol) and triethylamine (478.0 pL, 3.44 mmol) were added to a solution of compound 34-1 (500 mg, 2.65 mmol) in 10 mL of dichloromethane. The reaction solution was stirred at 25°C for 12 hours. After the reaction was completed, the reaction solution was quenched with 30 mL of aqueous sodium hydroxide solution (1 N), and the aqueous phase was extracted with dichloromethane (20 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 34-2. 1H NMR (400 MHz, CDCI3): J 8.79 (s, 2H), 8.14 (dd, J = 1.2, 8.0 Hz, 2H), 7.63 - 7.56 (m, 1H), 7.50 - 7.44 (m, 2H), 5.53 (s, 2H); m / z (ESI): [M + H] + = 294.4. Preparation of compound 34-3 Under a nitrogen atmosphere, caesium carbonate (607.20 mg, 1.86 mmol), (±)-2,2-bis(diphenylphosphino)-1,1-binaphthyl (178.53 mg, 0.29 mmol), palladium acetate (32.18 mg, 0.14 mmol), and benzophenone imine (312 mg, 1.72 mmol) were added to a solution of compound 34-2 (440 mg, 1.43 mmol) in 10 mL of toluene. The reaction solution was stirred at 120°C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, quenched with 60 mL of water, and extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain compound 34-3. 1H NMR (400 MHz, CDCl3): J 8.18 (s, 2H), 8.14 - 8.10 (m, 2H), 7.81 - 7.74 (m, 2H), 7.58 - 7.55 (m, 1H), 7.52 (d, J = 7.2 Hz, 1H), 7.48 - 7.42 (m, 4H), 7.38 -7.32 (m, 3H), 7.13 (dd, J = 2.0, 7.2 Hz, 2H), 5.47 (s, 2H); m / z (ESI): [M + H] + = 394.1. Preparation of compound 34-4 Under a nitrogen atmosphere, hydroxylamine hydrochloride (250.83 mg, 3.61 mmol) and sodium acetate (434.27 mg, 5.29 mmol) were added to a solution of compound 34-3 (600 mg, 1.20 mmol) in 10 mL of methanol. The reaction solution was stirred at 25°C for 7 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1 - 1 / 1) to obtain compound 34-4. 1H NMR (400 MHz, CDCl3): J 8.22 (s, 2H), 8.12 (d, J = 7.2 Hz, 2H), 7.60 -7.54 (m, 1H), 7.48 - 7.41 (m, 2H), 5.47 (s, 2H); m / z (ESI): [M + 23] + = 252.1. Preparation of compound 34-5 Under a nitrogen atmosphere,    2-(7-azobenzotriazole)-N,N,N',N'- tetramethyluronium hexafluorophosphate (120.62 mg, 0.32 mmol), N,N-diisopropylethylamine (69.9 pL, 0.42 mmol), and compound 34-4 (64.93 mg, 0.25 mmol) were added to a solution of compound 21-4 (80 mg, 0.21 mmol) in 2 mL of N,N-dimethylformamide. The reaction solution was stirred at 25°C for 16 hours. After the reaction was completed, the reaction solution was quenched with 40 mL of water and extracted with ethyl acetate (30 mL x3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (petroleum ether / ethyl acetate = 5 / 1-3 / 1) to obtain compound 34-5. 1H NMR (400 MHz, CDCI3): 3 8.97 (s, 2H), 8.38 (s, 1H), 8.16 - 8.09 (m, 2H), 7.63 - 7.55 (m, 1H), 7.50 - 7.41 (m, 2H), 7.17 - 7.09 (m, 1H), 7.04 - 6.94 (m, 1H), 5.53 (s, 2H), 5.04 (d, J = 11.2 Hz, 1H), 4.93 - 4.87 (m, 1H), 4.83 - 4.78 (m, 1H), 4.26 (dd, J = 7.6, 11.2 Hz, 1H), 2.89 - 2.81 (m, 1H), 2.44 (t, J = 2.4 Hz, 1H), 1.70 (s, 3H), 0.84 - 0.79 (m, 3H); m / z (ESI): [M + H] + = 590.2. Preparation of example 34 Under a nitrogen atmosphere, lithium hydroxide (38.05 mg, 0.91 mmol) was added to a solution of compound 34-5 (110 mg, 0.18 mmol) in 3 mL of methanol. The reaction solution was stirred at 25°C for 1 hour. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain a crude product, which was purified and separated by reversed-phase preparative chromatography (Column: Waters Xbridge 150 x 25 mm x 5 um; Condition: water (NH4HCO3)-ACN; Begin B:23, End B:53; Gradient Time (min): 10; 100%B Hold Time (min):4, Flow Rate (ml / min): 25) to obtain example 34. 1H NMR (400 MHz, DMSO-d6): 3 10.46 (s, 1H), 8.98 (s, 2H), 7.27 - 7.16 (m, 2H), 5.26 (t, J = 6.0 Hz, 1H), 5.15 (d, J = 10.4 Hz, 1H), 4.98 - 4.85 (m, 2H), 4.55 (d, J = 6.0 Hz, 2H), 4.32 (dd, J = 7.2, 10.2 Hz, 1H), 3.67 (t, J = 2.0 Hz, 1H), 2.89 - 2.78 (m, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H] + = 486.1. Example 35 Preparation of compound 35-2 Under a nitrogen atmosphere, triethylamine (94.1 mg, 0.93 mmol), tert-butyldimethyl(2-propynyloxy)silane     (317     mg,     1.86     mmol), (diphenylphosphino)ferrocene palladium dichloride (13.6 mg, 0.02 mmol), and cuprous iodide (7.08 mg, 0.04 mmol) were sequentially added to a solution of compound 3-1 (110 mg, 0.19 mmol) in 2 mL of N,N-dimethylformamide. The reaction solution was stirred at 80°C for 48 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with 30 mL of water, and extracted with ethyl acetate (15 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (0.1% FA / ACN, 80% to 90% over 5 min) to obtain compound 35-2. m / z (ESI): [M- H]+ = 612.2 Preparation of example 35 Under a nitrogen atmosphere, compound 35-2 (14 mg, 0.02 mmol) was added to a solution of hydrogen chloride in methanol (2 M, 2 mL). The reaction solution was stirred at 25°C for 0.5 hours. After the reaction was completed, the reaction solution was concentrated to dryness to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography ((column: Phenomenex luna C18 150 x 25 mm x 10 um, 35% to 65% over 9 min) and (column: Waters Xbridge 150 x 25 mm x 5 um, 35% to 65% over 11 min)) to obtain example 35. 1H NMR (400 MHz, DMSO-d6): § 10.78 (br s, 1H), 8.47 (d, J = 5.2 Hz, 1H), 8.27 (s, 1H), 8.08 - 8.03 (m, 1H), 7.83 (d, J = 3.6 Hz, 1H), 7.60 (s, 1H), 7.52 - 7.45 (m, 1H), 7.30 (dd, J = 4.4, 8.5 Hz, 1H), 5.67 - 5.45 (m, 1H), 5.20 (d, J = 10.4 Hz, 1H), 4.42 (s, 2H), 4.36 (dd, J = 7.6, 10.3 Hz, 1H), 3.04 - 2.92 (m, 1H), 1.62 (s, 3H), 0.71 (d, J = 6.4 Hz, 3H); m / z (ESI): [M+ H]+ =498.2. Examples 36 and 37 21-5 Example 36 Example 37 Preparation of compound 36-2 Under a nitrogen atmosphere, compound 36-1 (35.34 mg, 0.25 mmol) was added to a solution of compound 21-5 (100 mg, 0.25 mmol) and triethylamine (105.1 gL, 0.76 mmol) in 2 mL of dichloromethane. The reaction solution was reacted at 25°C for 1 hour. After the reaction was completed, 3 mL of water was added to dilute and quench the reaction, and the aqueous phase was extracted with dichloromethane (10 mL x 3). The combined organic phases were washed with 5 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (0.1% formic acid system) to obtain compound 36-2. 1H NMR (400 MHz, CDCI3): 8 8.38 - 8.29 (m, 2H), 7.51 (d, J = 1.6 Hz, 1H), 7.09 (dd, J = 1.6, 5.6 Hz, 1H), 7.03 - 6.96 (m, 1H), 4.99 (d, J = 11.2 Hz, 1H), 4.92 -4.86 (m, 1H), 4.83 - 4.77 (m, 1H), 4.25 (dd, J = 7.8, 11.2 Hz, 1H), 2.88 - 2.77 (m, 1H), 2.54 (s, 3H), 2.38 (t, J = 2.4 Hz, 1H), 1.70 (s, 3H), 0.80 (dd, J = 1.6, 7.4 Hz, 3H); m / z (ESI): [M + H]+ = 501.1. Preparation of examples 36 and 37 Under a nitrogen atmosphere, iodobenzene diacetate (40.80 mg, 0.13 mmol) and ammonium acetate (7.39 mg, 0.10 mmol) were sequentially added to a solution of compound 36-2 (30 mg, 0.06 mmol) in 1 mL of methanol. The reaction solution was reacted at 25°C for 18 hours. After the reaction was completed, the reaction solution was concentrated to obtain a crude product, which was purified by reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x5 um; mobile phase: water(NH4HCO3)-ACN; B%: 43% - 63%, 25 min) to obtain a mixture of example 36 and example 37. The mixture was resolved by SFC (Column DAICEL CHIRALPAK AD (250 x 50 mm x 10 um); Condition: CO2-EtOH (0.1% NH3H2O); B%: 20-20; Gradient Time (min): 3.6; 100% B Hold Time (min): 0; FlowRate (ml / min): 120) to obtain two single isomers. Example 36 (retention time=1.273 minutes): 1H NMR (400 MHz, DMSO-d6): 8 10.88 (s, 1H), 8.57 (d, J = 5.6 Hz, 1H), 8.36 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 2.0, 5.6 Hz, 1H), 7.27 - 7.17 (m, 2H), 5.13 (d, J = 10.4 Hz, 1H), 4.95 - 4.89 (m, 2H), 4.37 - 4.30 (m, 2H), 3.64 (t, J = 2.4 Hz, 1H), 3.11 (d, J = 0.8 Hz, 3H), 2.84 (t, J = 7.2 Hz, 1H), 1.61 (s, 3H), 0.74 (d, J = 6.4 Hz, 3H); m / z (ESI): [M + H]+ = 532.1. Example 37 (retention time=1.420 minutes): 1H NMR (400 MHz, DMSO-d6): 8 10.89 (s, 1H), 8.57 (d, J = 5.6 Hz, 1H), 8.35 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 2.0, 5.6 Hz, 1H), 7.27 - 7.16 (m, 2H), 5.13 (d, J = 10.4 Hz, 1H), 4.92 (t, J = 2.8 Hz, 2H), 4.39 - 4.29 (m, 2H), 3.64 (t, J = 2.4 Hz, 1H), 3.11 (d, J = 0.8 Hz, 3H), 2.87 - 2.80 (m, 1H), 1.61 (s, 3H), 0.74 (d, J = 5.6 Hz, 3H); m / z (ESI): [M + H]+ = 532.2. Example 38 Preparation of example 38 Under a nitrogen atmosphere, tris(dibenzylideneacetone)dipalladium (7.74 mg, 0.01 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (4.89 mg, 0.01 mmol), and N,N-diisopropylethylamine (41.9 pL, 0.25 mmol) were sequentially added to a solution of compound 3-1 (50 mg, 0.08 mmol) and dimethylphosphine oxide (13.20 mg, 0.17 mmol) in 2 mL of dioxane solvent. The reaction solution was warmed to 100°C and stirred for 15 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and filtered through a short pad of silica gel (washed with ethyl acetate). The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x5 um; mobile phase: water(NH4HCO3)-ACN; B%: 23% - 53%, 25 min) to obtain example 38. 1H NMR (400 MHz, DMSO-d6): 8 10.60 (s, 1H), 8.48 (d, J = 5.5 Hz, 1H), 8.28 (d, J = 2.1 Hz, 1H), 8.06 (d, J = 2.1 Hz, 1H), 7.83 (dd, J = 2.2, 5.6 Hz, 1H), 7.72 -7.59 (m, 2H), 7.46 - 7.39 (m, 1H), 5.48 (dd, J = 7.1, 10.8 Hz, 1H), 5.15 (d, J = 10.8 Hz, 1H), 2.90 (t, J = 7.4 Hz, 1H), 1.85 - 1.76 (m, 6H), 1.58 (s, 3H), 0.76 (d, J = 6.5 Hz, 3H); m / z (ESI): [M + H] + = 520.2. Example 39 24-3                              Example 39 Preparation of example 39 Under a nitrogen atmosphere, triethylamine (139.4 pL, 1.00 mmol) was added to a solution of compound 24-3 (100 mg, 0.25 mmol) in 0.5 mL of dichloromethane, followed by the addition of 4-aminopyridine-2-sulphonamide (45.17 mg, 0.26 mmol). The mixture was stirred at 26°C for 2 hours. After the reaction was completed, the reaction solution was quenched with 20 mL of water, and extracted with dichloromethane (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (Column Waters Xbridge 150*25 mm* 5 um; mobile phase: water(NH3H2O)-ACN; B%: 38% - 68%, 12 min) to obtain example 39. 1H NMR (400 MHz, DMSO-d6): § 10.52 (s, 1H), 8.09 - 8.31 (m, 1H), 7.75 (dt, J = 7.6, 2.0 Hz, 1H), 7.44 - 7.61 (m, 2H), 7.36 (s, 2H), 7.08 - 7.28 (m, 2H), 5.10 (d, J = 10.4 Hz, 1H), 4.34 (dd, J = 10.32, 7.44 Hz, 1H), 3.64 (s, 1H), 2.85 (s, 1H), 1.62 (s, 3H), 0.63 - 0.83 (m, 3H); m / z (ESI): [M+H] + = 535.2. Example 40 24-3                                40-2                              Example 40 Preparation of compound 40-2 Under a nitrogen atmosphere, triethylamine (57.5 pL, 0.41 mmol) and compound 40-1 (43.28 mg, 0.21 mmol) were added to a solution of compound 24-3 (55.0 mg, 0.14 mmol) in 1 mL of dichloromethane. The reaction solution was reacted at 25°C for 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3 / 1) to obtain compound 40-2. 1H NMR (400 MHz, CDCI3): 3 8.51 (s, 1H), 7.82 - 7.77 (m, 3H), 7.20 - 7.12 (m, 1H), 7.03 - 6.94 (m, 1H), 5.02 (d, J = 11.2 Hz, 1H), 4.26 (dd, J = 7.6, 11.2 Hz, 1H), 3.90 (s, 3H), 3.89 (s, 3H), 2.90 - 2.78 (m, 1H), 2.37 (s, 1H), 1.71 (s, 3H), 0.85 - 0.78 (m, 3H); m / z (ESI): [M+H] + = 572.2. Preparation of example 40 Under a nitrogen atmosphere, compound 40-2 (50.0 mg, 0.08 mmol) was dissolved in 5 mL of ammonia solution in methanol (7 M). The reaction solution was reacted at 60°C for 17 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (Column Phenomenex luna C18 150 x 25 mm x 10 um; mobile phase: water(FA)-ACN; B%: 43% - 73%, 11 min) to obtain example 40. 1H NMR (400 MHz, METHANOL-d4): 3 8.54 (s, 1H), 7.82 (d, J = 2.0 Hz, 1H), 7.73 (dd, J = 2.0, 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.23 - 7.13 (m, 1H), 7.09 -6.99 (m, 1H), 5.08 (d, J = 10.8 Hz, 1H), 4.43 (dd, J = 8.0, 10.2 Hz, 1H), 2.93 (s, 1H), 2.90 - 2.84 (m, 1H), 1.68 (s, 3H), 0.83 (d, J = 5.6 Hz, 3H); m / z (ESI): [M+H] +=542.2. Example 41 24-5                         Example 41 Preparation of example 41 Under a nitrogen atmosphere, m-chloroperoxybenzoic acid (55.0 mg, 0.32 mmol) was added to a solution of compound 24-5 (80 mg, 0.16 mmol) in 3 mL of dichloromethane at 0°C. The reaction solution was stirred at 0°C for 2 hours. After the reaction was completed, the reaction solution was quenched by slow addition to 50 mL of saturated aqueous sodium sulphite solution. After a negative result with starch-potassium iodide test paper was obtained in the aqueous phase, the mixture was extracted with dichloromethane (20 mL x 2). The combined organic phases were washed with 20 mL of saturated sodium bicarbonate solution, dried over anhydrous sodium sulphate, filtered, and concentrated to obtain a crude product, which was separated and purified by reversed-phase preparative chromatography (column: Waters Xbridge C18 150*25 mm*5 um; mobile phase: [A: H2O(10 mM NH4HCO3);B: ACN]; B%: 48.00%-78.00%, 15.00 min; flow rate: 25.00 ml / min) to obtain example 41. 1H NMR (400 MHz, DMSO-d6): 3 10.90 (s, 1H), 8.63 (d, J = 5.6 Hz, 1H), 8.36 (d, J = 2.0 Hz, 1H), 7.91 (dd, J = 2.0, 5.6 Hz, 1H), 7.30 - 7.15 (m, 2H), 5.14 (d, J = 10.4 Hz, 1H), 4.33 (dd, J = 7.6, 10.4 Hz, 1H), 3.62 (s, 1H), 3.24 (s, 3H), 2.90 - 2.77 (m, 1H), 1.62 (s, 3H), 0.74 (d, J = 6.4 Hz, 3H); m / z (ESI): [M+ H] + = 535.2. Example 42 Preparation of compound 42-2 Under a nitrogen atmosphere, compounds dimethylphosphine oxide (676.69 mg, 8.67 mmol), potassium phosphate (3.07 g, 14.45 mmol), tris(dibenzylideneacetone)dipalladium (317.58 mg, 0.35 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (401.34 mg, 0.69 mmol) were added to a solution of compound 42-1 (1.0 g, 5.78 mmol) in 20 mL of N,N-dimethylformamide. The reaction solution was warmed to 140°C and reacted for 16 hours. After the reaction was completed, the reaction solution was cooled to room temperature and filtered, and the filter cake was washed twice with 10 mL of ethyl acetate. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated by silica gel column chromatography (dichloromethane / methanol = 10 : 1) to obtain compound 42-2. 1H NMR (400 MHz, DMSO-d6): S 8.09 (d, J = 5.6 Hz, 1H), 7.10 (dd, J = 2.4, 7.2 Hz, 1H), 6.52 (td, J = 2.0, 5.6 Hz, 1H), 6.34 (s, 2H), 1.56 (s, 3H), 1.53 (s, 3H); m / z (ESI): [M + H] + = 171.2. Preparation of example 42 Under a nitrogen atmosphere, compound 42-2 (42.93 mg, 0.21 mmol) and triethylamine (57.5 pL, 0.41 mmol) were sequentially added to a solution of compound 24-3 (55 mg, 0.14 mmol) in 1 mL of dichloromethane. The reaction solution was reacted at 25°C for 1 hour. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (chromatographic column Waters Xbridge C18 150 x 25 mm x 5 um, aqueous phase - organic phase H2O(10 mM NH4HCO3)-ACN, B%: 33% - 63%, 15 min) to obtain example 42. 1H NMR (400 MHz, DMSO-d6): S 10.74 (s, 1H), 8.61 (d, J = 5.6 Hz, 1H), 8.21 (dd, J = 2.0, 6.4 Hz, 1H), 7.77 (td, J = 2.0, 5.6 Hz, 1H), 7.27 - 7.13 (m, 2H), 5.12 (d, J = 10.6 Hz, 1H), 4.33 (dd, J = 7.2, 10.2 Hz, 1H), 3.65 (s, 1H), 2.91 - 2.77 (m, 1H), 1.70 - 1.51 (m, 9H), 0.74 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H] + = 533.2. Example 43 Preparation of compound 43-3 Under a nitrogen atmosphere, compound 43-2 (2.69 g, 20.34 mmol), triphenylphosphine (5.34 g, 20.34 mmol), and diisopropyl azodicarboxylate (4.0 mL, 20.34 mmol) were added to a solution of compound 43-1 (1.9 g, 13.56 mmol) in 30 mL of toluene. The reaction solution was warmed to 80°C and reacted for 3 hours. After the reaction was completed, the reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (petroleum ether / ethyl acetate = 10: 1) to obtain compound 43-3. 1H NMR (400 MHz, CDCI3): 3 8.39 (d, J = 5.6 Hz, 1H), 7.61 (dd, J = 2.0, 5.6 Hz, 1H), 7.53 (d, J = 2.0 Hz, 1H), 4.57 - 4.39 (m, 3H), 4.17 (dd, J = 6.4, 8.4 Hz, 1H), 3.88 (dd, J = 6.0, 8.4 Hz, 1H), 1.47 (s, 3H), 1.41 (s, 3H). Preparation of compound 43-4 Under a nitrogen atmosphere, iron powder (2.42 g, 43.42 mmol) and ammonium chloride (2.32 g, 43.42 mmol) were added to a solution of compound 43-3 (2.3 g, 8.68 mmol) in 20 mL of ethanol and 4 mL of water. The reaction solution was warmed to 80°C and reacted for 2 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with 40 mL of ethyl acetate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1-1 / 1) to obtain compound 43-4. 1H NMR (400 MHz, DMSO-d6): 3 7.59 (d, J = 6.0 Hz, 1H), 6.17 (dd, J = 2.0, 6.0 Hz, 1H), 5.93 (s, 2H), 5.81 (d, J = 1.6 Hz, 1H), 4.37 - 4.29 (m, 1H), 4.20 - 4.09 (m, 2H), 4.03 (dd, J = 6.4, 8.0 Hz, 1H), 3.69 (dd, J = 6.4, 8.0 Hz, 1H), 1.33 (s, 3H), 1.28 (s, 3H); m / z (ESI): [M + H] + = 225.2. Preparation of compound 43-5 Under a nitrogen atmosphere, compound 43-5 (86.97 mg, 0.38 mmol) and triethylamine (104.6 pL, 0.75 mmol) were added to a solution of compound 24-3 (100 mg, 0.25 mmol) in 1 mL of dichloromethane. The reaction solution was reacted at 25°C for 1 hour. After the reaction was completed, the reaction solution was quenched with 20 mL of water, and extracted with dichloromethane (20 mL x 2). The combined organic phases were dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product, which was separated by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1-3 / 1) to obtain compound 43-5. 1H NMR (400 MHz, CDCI3): S 8.37 (s, 1H), 8.03 (d, J = 6.4 Hz, 1H), 7.17 -7.10 (m, 1H), 7.06 - 6.95 (m, 3H), 4.98 (d, J = 11.2 Hz, 1H), 4.49 - 4.42 (m, 1H), 4.37 - 4.30 (m, 2H), 4.25 (dd, J = 8.0, 11.3 Hz, 1H), 4.12 (dd, J = 6.0, 8.4 Hz, 1H), 3.85 (dd, J = 6.0, 8.4 Hz, 1H), 2.89 - 2.77 (m, 1H), 2.37 (s, 1H), 1.69 (s, 3H), 1.45 (s, 3H), 1.39 (s, 3H), 0.83 - 0.78 (m, 3H); m / z (ESI): [M + H] + = 587.2. Preparation of example 43 Under a nitrogen atmosphere, trifluoroacetic acid (0.2 mL, 2.69 mmol) was added to a solution of compound 43-5 (50 mg, 0.08 mmol) in 2 mL of dichloromethane. The reaction solution was reacted at 26°C for 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (column: Waters Xbridge C18 150*25 mm*5 um; mobile phase: [A: H2O (10 mM NH4HCO3); B: ACN]; B%: 40.00%-70.00%, 15.00 min; flow rate: 25.00 ml / min) to obtain example 43. 1H NMR (400 MHz, DMSO-d6): S 10.49 (s, 1H), 8.01 (d, J = 5.6 Hz, 1H), 7.26 - 7.19 (m, 1H), 7.17 - 7.10 (m, 3H), 5.08 (d, J = 10.4 Hz, 1H), 4.87 (d, J = 5.2 Hz, 1H), 4.60 (t, J = 5.6 Hz, 1H), 4.32 (dd, J = 7.6, 10.0 Hz, 1H), 4.22 (dd, J = 4.4, 10.8 Hz, 1H), 4.09 (dd, J = 6.0, 10.8 Hz, 1H), 3.75 (qd, J = 5.6, 10.8 Hz, 1H), 3.63 (s, 1H), 3.40 (t, J = 5.6 Hz, 2H), 2.90 - 2.77 (m, 1H), 1.59 (s, 3H), 0.73 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H]+ = 547.2. Example 44 24-3                                    Example 44 Preparation of example 44 Under a nitrogen atmosphere, compound 24-3 (424 mg, 1.06 mmol) was dissolved in dichloromethane (6 mL), and triethylamine (0.5 mL, 3.6 mmol) was added, followed by the addition of compound 44-1 (127 mg, 1.06 mmol). The reaction solution was stirred at room temperature for 3 hours. After the reaction was completed, the reaction solution was quenched with 20 mL of saturated aqueous sodium bicarbonate solution, and the aqueous phase was extracted with dichloromethane (3 x 20 mL). The combined organic phases were washed with saturated sodium chloride aqueous solution (1 x 30 mL), dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure. The crude product was separated and purified by column chromatography (petroleum ether / ethyl acetate = 10 / 1-1 / 1) to obtain example 44. LC-MS (ESI): [M + H] + = 482.1. Example 45 24-3                           Example 45 Preparation of example 45 Compound 45-1 (17.95 mg, 0.16 mmol) and triethylamine (87.1 pL, 0.63 mmol) were dissolved in DMF (1 mL). The mixture was stirred at room temperature for 5 minutes, and a solution of compound 24-3 (50 mg, 0.13 mmol) in DMF (1 mL) was slowly added dropwise. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, water (10 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 ml x 3). The organic phases were washed with saturated aqueous sodium chloride solution (10 ml x 3), dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by preparative silica gel thin-layer chromatography (dichloromethane : methanol = 10 : 1) and reversed-phase preparative chromatography (Phenomenex luna C18 150x25 mm x 10 um); flow rate: 25 mL / min; gradient: 47% - 67% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 45. 1H NMR (400 MHz, CDCI3): 3 8.42 - 8.27 (m, 1H), 7.15 - 6.94 (m, 3H), 6.75 -6.62 (m, 2H), 5.06 - 4.93 (m, 1H), 4.36 - 4.20 (m, 1H), 2.88 - 2.78 (m, 1H), 2.47 -2.40 (m, 1H), 1.36 - 1.18 (m, 3H), 0.80 (d, J = 5.2 Hz, 3H); m / z (ESI): [M + H]+ = 473.1. Example 46 Preparation of example 46 Under a nitrogen atmosphere, a solution of sodium methoxide in methanol (0.01 mL, 0.05 mmol) was added to a solution of example 44 (100 mg, 0.21 mmol) in 5 mL of methanol. The reaction solution was stirred at room temperature for 2 hours, and then ammonium chloride (23 mg, 0.42 mmol) was added. The mixture was warmed to 40°C and stirred for another 12 hours. The reaction solution was concentrated, and the crude product was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150*25 mm * 10 um); flow rate: 25 mL / min; gradient: 23% - 53% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 46. 1H NMR (400 MHz, DMSO-d6): 8 8.61 (d, J = 5.6 Hz, 1H), 8.47 - 8.44 (m, 2H), 7.89 - 7.87 (m, 1H), 7.23 - 7.21 (m, 2H), 5.19 (d, J = 10.8 Hz, 1H), 4.38 - 4.33 (m, 1H), 3.66 (s, 1H), 2.89 - 2.81 (m, 1H), 1.62 (s, 3H), 0.75 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H]+ = 499.1. Example 47 Preparation of example 47 Under a nitrogen atmosphere, example 44 (100 mg, 0.21 mmol) was dissolved in 2 mL of 1,4-dioxane. Triethylamine (0.058 mL, 0.42 mmol) and dimethylamine hydrochloride (33.87 mg, 0.42 mmol) were sequentially added. The reaction solution was warmed to 90°C and stirred for 16 hours. The reaction solution was concentrated, and the crude product was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150x25 mm x 10 um); flow rate: 25 mL / min; gradient: 24% - 54% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 47. 1H NMR (400 MHz, DMSO-d6): 3 11.55 - 11.48 (m, 1H), 8.57 (d, J = 5.6 Hz, 1H), 8.44 (s, 1H), 8.04 (d, J = 1.6 Hz, 1H), 7.78 - 7.76 (m, 1H), 7.30 - 7.26 (m, 1H), 7.23 - 7.17 (m, 1H), 5.26 (d, J = 10.4 Hz, 1H), 4.37 - 4.33 (m, 1H), 3.66 (s, 1H), 3.02 (s, 6H), 2.87 - 2.78 (m, 1H), 1.61 (s, 3H), 0.75 (d, J = 6.4 Hz, 3H); m / z (ESI): [M + H]+ = 527.2. Example 48 Preparation of compound 48-1 Compound 12-2 (500 mg, 3.85 mmol), imidazole (800 mg, 11.76 mmol), and tert-butyldiphenylchlorosilane (2.4 g, 8.73 mmol) were dissolved in anhydrous DCM (30 mL), and the mixture was stirred at room temperature for 12 hours. The reaction solution was concentrated to obtain a crude product, which was purified by silica gel column chromatography (eluting with petroleum ether) to obtain compound 48-1. Preparation of compound 48-2 Compound 48-1 (900 mg, 2.44 mmol) and potassium carbonate (1.1 g, 7.96 mmol) were dissolved in DMF (12 mL), and the mixture was stirred at room temperature for 24 hours. Ethyl acetate (100 mL) was added to the reaction solution, and the mixture was washed once with water (30 mL) and once with saturated sodium chloride aqueous solution (30 mL). The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation. The mixture was purified by silica gel column chromatography to obtain compound 48-2. 1H NMR (400 MHz, CDC13): 3 756 - 7.59 (m, 1H), 7.26 - 7.50 (m, 1H), 2.24 (s, 1H),1.12 - 1.34 (m, 9H). Preparation of compound 48-3 Under a nitrogen atmosphere, compound 48-2 (370 mg, 1.25 mmol) was dissolved in THF (1 mL) at -50°C. A solution of n-butyllithium in n-hexane (1.0 mL, 2.50 mmol) was slowly added, and the mixture was stirred for 0.5 hours. A solution of deuterated iodomethane (370 mg, 2.55 mmol) in THF (1 mL) was added, and the mixture was stirred for 1 hour. The reaction solution was poured into saturated aqueous ammonium chloride solution (100 mL) to quench the reaction, and the mixture was extracted with ethyl acetate (100 mL x 3). The organic phases were combined, washed once with saturated sodium chloride aqueous solution (100 mL), dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation to obtain compound 48-3. 1H NMR (400 MHz, CDCI3): 3 7.77 - 7.79 (m, 1H), 7.44 - 7.50 (m, 1H), 1.12 -1.34 (m, 9H). Preparation of compound 48-4 Compound 48-3 (370 mg, 1.18 mmol) was dissolved in a solution of tetrabutylammonium fluoride in tetrahydrofuran (5 mL, 5.00 mmol), and the mixture was stirred at room temperature for 0.5 hours. The reaction solution was diluted with ethyl acetate (100 mL), and washed once with water (100 mL) and once with saturated sodium chloride aqueous solution (100 mL). The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation to obtain compound 48-4. Preparation of example 48 Under a nitrogen atmosphere, triphenylphosphine (70 mg, 0.11 mmol), compound 1-18 (50 mg, 0.11 mmol), and compound 48-4 (10 mg, 0.13 mmol) were dissolved in THF (1.5 mL). Diisopropyl azodicarboxylate (30 mg, 0.15 mmol) was added in an ice-water bath, and the mixture was stirred at room temperature overnight. Ethyl acetate (20 mL) was added to the reaction solution, and the mixture was washed with water (10 mL x2) and saturated sodium chloride aqueous solution (10 mL) once. The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation to obtain a crude product, which was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150^25 mm x 10 um); flow rate: 25 mL / min; gradient: 48% - 78% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 48. m / z (ESI): [M + H]+ = 517.1. Example 49 Example 24                               Example 49 Preparation of example 49 Example 24 (50 mg, 0.09 mmol) was placed in a 50 mL single-necked flask. DCM (3 mL) was added at room temperature, and the system was purged with argon. Trimethyloxonium tetrafluoroborate (7 mg, 0.05 mmol) was added to the solution, and the mixture was stirred at room temperature for 6 hours. The reaction solution was concentrated to dryness by rotary evaporation to obtain a crude product, which was purified by silica gel thin-layer chromatography (petroleum ether : ethyl acetate =1 : 1) to obtain example 49. 1H NMR (400 MHz, DMSO-d6): 8 10.91 (s, 1H), 8.62 (d, J = 5.5 Hz, 1H), 8.32 (d, J = 1.9 Hz, 1H), 7.86 (dd, J = 5.5, 2.1 Hz, 1H), 7.32 - 7.12 (m, 2H), 5.14 (d, J = 10.4 Hz, 1H), 4.34 (dd, J = 10.4, 7.5 Hz, 1H), 3.63 (s, 1H), 3.16 (s, 3H), 2.93 - 2.76 (m, 1H), 2.45 (s, 3H), 1.62 (s, 3H), 0.74 (d, J = 6.2 Hz, 3H); m / z (ESI): [M + H]+ = 548.4. Example 50 Example 50 Preparation of compound 50-1 Under a nitrogen atmosphere, a solution of boron tribromide in dichloromethane (12.7 mL, 25.4 mmol) was slowly added dropwise to a solution of compound 1-12 (4.5 g, 12.7 mmol) in 60 mL of dichloromethane at 0°C. The reaction solution was warmed to 25°C and stirred for 1 hour. After the reaction was completed, the reaction solution was poured into 100 mL of saturated aqueous sodium bicarbonate solution. The mixture was extracted with 50 mL of dichloromethane once, and the organic phase was discarded. The aqueous phase was adjusted to pH 3-4 with dilute hydrochloric acid (30 mL, 3 M) and extracted with dichloromethane (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain compound 50-1. 1H NMR (400 MHz, DMSO-d6): 5 7.11 - 6.96 (m, 1H), 6.92 - 6.70 (m, 1H), 4.97 (d, J = 10.4 Hz, 1H), 4.09 (dd, J = 10.4, 7.6 Hz, 1H), 2.73 (s, 1H), 1.52 (s, 3H), 0.67 (d, J = 6.0 Hz, 3H). Preparation of compound 50-2 Under               a               nitrogen               atmosphere, 2,2,2-trichloro-1-[(2-methylpropan-2-yl)oxy]ethan-1-imine (10.82 g, 49.52 mmol) was added to a solution of compound 50-1 (3.37 g, 9.90 mmol) in 35 mL of dichloromethane. The reaction solution was stirred at 25°C for 1 hour. After the reaction was completed, the reaction solution was quenched with 20 mL of water, and extracted with dichloromethane (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - 5 / 1) to obtain compound 50-2. 1H NMR (400 MHz, DMSO-d6): 5 7.04 (t, J = 6.8 Hz, 1H), 6.91 - 6.74 (m, 1H), 4.90 (d, J = 10.4 Hz, 1H), 4.04 (dd, J = 10.8, 7.2 Hz, 1H), 2.70 (t, J = 7.6 Hz, 1H), 1.52 (d, J = 2.0 Hz, 5H), 1.27 (s, 9H), 0.70 (d, J = 5.6 Hz, 3H). Preparation of compound 50-3 Under a nitrogen atmosphere, trifluoromethanesulphonic anhydride (4.409 g, 15.63 mmol) was added to a solution of triethylamine (3.163 g, 31.26 mmol) and compound 50-2 (4.130 g, 10.42 mmol) in 40 mL of dichloromethane at 0°C. The reaction solution was reacted at 0°C for 2 hours. After the reaction was completed, the reaction solution was poured into 100 mL of water, and the aqueous phase was extracted with dichloromethane (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1 - 2 / 1) to obtain compound 50-3. 1H NMR (400 MHz, CDCI3): 3 7.35 - 7.13 (m, 2H), 4.79 (d, J = 9.6 Hz, 1H), 4.23 - 4.03 (m, 1H), 2.78 (t, J = 7.6 Hz, 1H), 1.63 (s, 3H), 1.35 (s, 9H), 1.23 - 1.30 (m, 2H), 0.90 - 0.78 (m, 3H). Preparation of compound 50-4 Under a nitrogen atmosphere, potassium vinyltrifluoroborate (2.23 g, 16.65 mmol), caesium carbonate (5.426 g, 16.65 mmol) and RuPhos Pd G3 (696 mg, 0.83 mmol) were sequentially added to a solution of compound 50-3 (4.4 g, 8.33 mmol) in 9 mL of water and 45 mL of toluene. The reaction solution was warmed to 85°C and reacted for 5 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and diluted with 50 mL of water. The aqueous phase was extracted with ethyl acetate (50 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1 - 5 / 1) to obtain compound 50-4. 1H NMR (400 MHz, CDCl3): 3 7.15 - 6.98 (m, 2H), 6.56 (dd, J = 17.6, 11.6 Hz, 1H), 5.84 - 5.46 (m, 2H), 4.89 - 4.75 (m, 2H), 4.06 - 3.94 (m, 1H), 2.58 (s, 1H), 1.56 (s, 3H), 1.31 (s, 9H), 1.29 - 1.27 (m, 1H). 0.81 - 0.72 (m, 3H). Preparation of compound 50-5 A solution of compound 50-4 (3.287 g, 8.09 mmol) in 50 mL of dichloromethane was aerated with ozone until the reaction solution turned blue. The solution was purged with nitrogen until the yellow colour returned. Triphenylphosphine (3.18 g, 12.13 mmol) was added, and the reaction solution was slowly warmed to 25°C and reacted for 12 hours. After the reaction was completed, the reaction solution was concentrated to dryness by rotary evaporation under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20 / 1 - 10 / 1) to obtain compound 50-5. 1H NMR (400 MHz, CDCI3): 3 10.52 (s, 1H), 7.47 - 7.38 (m, 1H), 7.27 (s, 2H), 4.88 (d, J = 10.6 Hz, 1H), 4.76 - 4.63 (m, 1H), 2.87 (s, 1H), 1.68 (s, 3H), 1.32 (s, 9H), 0.78 - 0.69 (m, 3H). Preparation of compound 50-6 Under a nitrogen atmosphere, sodium borohydride (92.64 mg, 2.45 mmol) was slowly added to a solution of compound 50-5 (0.5 g, 1.22 mmol) in 6 mL of tetrahydrofuran at 0°C. The reaction solution was warmed to 25°C and stirred for 1 hour. After the reaction was completed, the reaction solution was quenched with 10 mL of saturated aqueous ammonium chloride solution. The aqueous phase was extracted with ethyl acetate (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - 5 / 1) to obtain compound 50-6. Preparation of compound 50-7 Under a nitrogen atmosphere, sodium hydride (102 mg, 2.56 mmol, 60% content) was slowly added to a solution of compound 50-6 (350 mg, 0.85 mmol) in 6 mL of tetrahydrofuran at 0°C. The mixture was stirred for 10 minutes, and then (3-bromoprop-1-ynyl)trimethylsilane (244 mg, 1.28 mmol) was added, and the reaction solution was warmed to 25°C and stirred for 6 hours. After the reaction was completed, the reaction solution was quenched with 5 mL of saturated aqueous ammonium chloride solution, and adjusted to pH = 3-4 with 0.5 M hydrochloric acid. The aqueous phase was extracted with dichloromethane (10 mL x 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - 1 / 1) to obtain compound 50-7. Preparation of compound 50-8 Under a nitrogen atmosphere, N,N-dimethylformamide (2.3 gL, 0.03 mmol) and oxalyl chloride (114.52 mg, 0.90 mmol) were sequentially added to a solution of compound 50-7 (118 mg, 0.30 mmol) in 4 mL of dichloromethane solvent. The reaction solution was reacted at 25°C for 1 hour to provide a solution containing compound 50-8, which was directly used in the next step. Preparation of compound 50-9 Under a nitrogen atmosphere, triethylamine (416.2 pL, 2.99 mmol) was added to the reaction solution from the previous step (pH > 8), followed by the addition of methyl 4-aminopyridine-2-carboxylate (136.68 mg, 0.90 mmol). The reaction solution was stirred at 25°C for 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude product, which was separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1 - 1 / 2) to obtain compound 50-9. Preparation of example 50 Under a nitrogen atmosphere, compound 50-9 (74 mg, 0.14 mmol) was added to a 7.0 M ammonia solution in methanol (3 mL, 21 mmol). The reaction solution was reacted at 25°C for 12 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude product, which was purified by reversed-phase preparative chromatography (column: Boston Green ODS 150*30 mm*5 um; mobile phase: [A: H2O (0.225% FA); B: ACN]; B%: 48.00%-78.00%, 11.00 min; flow rate: 25.00 mL / min) to obtain example 50. 1H NMR (400 MHz, DMSO-d6): £ 10.62 (s, 1H), 8.48 (d, J = 5.6 Hz, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.05 (s, 1H), 7.81 (dd, J = 5.6, 2.0 Hz, 1H), 7.60 (d, J = 2.0 Hz, 1H), 7.51 - 7.37 (m, 1H), 7.35 - 7.23 (m, 1H), 5.16 (d, J = 10.8 Hz, 1H), 4.65 (d, J = 2.0 Hz, 2H), 4.40 - 4.30 (m, 1H), 4.24 (dd, J = 4.4, 2.4 Hz, 2H), 3.55 (s, 1H), 3.52 - 3.49 (m, 1H), 2.82 (s, 1H), 1.64 (s, 3H), 0.83 - 0.64 (m, 3H); m / z (ESI): [M + H]+ = 512.1. Example 51 1-18                            Example 51 Preparation of example 51 Compound 1-18 (200 mg, 0.44 mmol) was dissolved in DMF (2 mL). Potassium carbonate (180.50 mg, 1.31 mmol), chloromethyl methyl sulphide (126.13 mg, 1.31 mmol), and potassium iodide (72.27 mg, 0.44 mmol) were added, and the mixture was reacted at 25°C for 1 hour. The reaction solution was added to 20 mL of water, and the mixture was extracted with dichloromethane and subjected to liquid separation. The organic phase was washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation. The crude product was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150x25 mm x 10 um); flow rate: 25 mL / min; gradient: 52% - 72% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 51. 1H NMR (400 MHz, DMSO-d6): 8 10.71 (s, 1H), 8.49 (d, J = 6.0 Hz, 1H), 8.27 (d, J = 2.4 Hz, 1H), 8.07 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 2.0, 5.6 Hz, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.21 (d, J = 6.4 Hz, 2H), 5.48 - 5.38 (m, 1H), 5.37 - 5.31 (m, 1H), 5.12 (d, J = 10.4 Hz, 1H), 4.38 (dd, J = 7.6, 10.0 Hz, 1H), 2.83 (t, J = 7.6 Hz, 1H), 2.22 (s, 3H), 1.62 (s, 3H), 0.73 (d, J = 6.0 Hz, 3H); m / z (ESI): [M + H]+ = 520.1. Example 52 1-18 Example 52 Preparation of example 52 Compound 52-1 (70 mg, 0.26 mmol), compound 1-18 (120 mg, 0.26 mmol), potassium carbonate (110 mg, 0.80 mmol), and sodium iodide (50 mg, 0.33 mmol) were dissolved in DMF (5 mL), and the mixture stirred at room temperature for 12 hours. The reaction solution was poured into water (100 mL) to quench the reaction, and the mixture was extracted with ethyl acetate (100 mL x 2). The organic phase was washed with saturated sodium chloride aqueous solution (100 mL), dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation. The crude product was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150x25 mm x 10 um); flow rate: 25 mL / min; gradient: 45% - 75% B over 15 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 52. 1H NMR (400 MHz, DMSO-d6): 8 10.72 (s, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.08 (s, 1H), 7.84 (dd, J = 2.0, 5.6 Hz, 1H), 7.64 (s, 1H), 7.61 - 7.52 (m, 1H), 7.43 - 7.35 (m, 1H), 5.17 (d, J = 10.2 Hz, 1H), 4.79 - 4.71 (m, 1H), 4.26 - 4.18 (m, 1H), 2.73 - 4.64 (m, 1H), 1.60 (s, 3H), 0.78 - 0.70 (m, 3H); m / z (ESI): [M + H]+ = 534.0. Examples 53 and 54 Preparation of compound 53-1 A solution of ethynylmagnesium bromide in tetrahydrofuran (1.9 mL, 0.96 mmol, 0.5 M) was slowly added dropwise to a solution of 50-5 (300 mg, 0.73 mmol) in THF (10 mL) at 0°C. The reaction solution was allowed to naturally warm from 0°C to 25°C and stirred for 2 hours. After the reaction was completed, the reaction was quenched by slow dropwise addition of aqueous ammonium chloride solution (3 mL) to the reaction solution at 0°C. The mixture was diluted with water (10 ml), and extracted with ethyl acetate (10 ml x 3). The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 5 : 1-3 : 1) to obtain compound 53-1. Preparation of compound 53-2 Diethylaminosulphur trifluoride (0.1 mL, 607.73 pmol) was slowly added dropwise to a solution of 53-1 (220 mg, 506.45 pmol) in DCM (5 mL) at -20°C. The reaction solution was allowed to naturally warm from 0°C to 25°C and reacted for 2 hours. The reaction was quenched by slow dropwise addition of the reaction solution to saturated sodium bicarbonate solution, and the mixture was extracted with dichloromethane (5 mLx3). The organic phase was dried and concentrated, and the crude product was purified by silica gel column chromatography (petroleum ether : ethyl acetate=10 : 1-3 : 1) to obtain compound 53-2. Preparation of compound 53-3 Compound 53-2 (195 mg, 0.45 mmol) was dissolved in DCM (5 mL). Trifluoroacetic acid (1 mL) was added, and the mixture was reacted at 25°C for 1 hour. The reaction solution was concentrated directly to obtain compound 53-3. Preparation of compound 53-4 Compound 53-3 (150 mg, 0.39 mmol) and DMF (3.1 gL, 0.04 mmol) were dissolved in DCM (5 mL). Oxalyl chloride (169.4 gL, 1.97 mmol) was slowly added in an ice bath, and the reaction solution was stirred at room temperature for 3 hours. The reaction solution was concentrated to obtain compound 53-4. Preparation of compound 53-5 Compound 53-4 (140 mg, 0.35 mmol) was dissolved in DCM (0.5 mL). Triethylamine (0.2 mL, 1.76 mmol) and methyl 4-aminopyridine-2-carboxylate (53.42 mg, 0.35 mmol) were slowly added in an ice bath, and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated, and the crude product was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 1 : 1) to obtain compound 53-5. Preparation of examples 53 and 54 Compound 53-5 (20 mg, 0.04 mmol) and ammonia in methanol (16.55 mg, 0.97 mmol) were dissolved in MeOH (0.5 mL). The reaction solution was stirred at 25°C for 3 hours. The reaction solution was concentrated, and the crude product was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150 x2 5 mm x 10 um); flow rate: 25 mL / min; gradient: 49% - 69% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile)) to obtain two isomers. Example 53 (shorter retention time): 1H NMR (400 MHz, DMSO-d6): S 10.56 (s, 1H), 8.48 (d, J = 5.6 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 2.4 Hz, 1H), 7.82 (dd, J = 2.0, 5.2 Hz, 1H), 7.67 -7.56 (m, 2H), 7.40 - 7.35 (m, 1H), 6.85 - 6.69 (m, 1H), 5.16 (d, J = 10.0 Hz, 1H), 4.46 (t, J= 9.2 Hz, 1H), 4.28 (dd, J = 2.0, 5.0 Hz, 1H), 2.94 - 2.85 (m, 1H), 1.66 (s, 3H), 0.76 (d, J = 7.2 Hz, 3H); m / z (ESI): [M + H]+ = 500.2. Example 54 (longer retention time): 1H NMR: (400 MHz, DMSO-d6): S 10.58 (s, 1H), 8.48 (d, J = 5.2Hz, 1H), 8.27 (d, J =2.0 Hz, 1H), 8.06 (d, J = 1.2 Hz, 1H), 7.86 (dd, J = 2.2, 5.6 Hz, 1H), 7.65 - 7.56 (m, 2H), 7.40 (dd, J = 4.2, 8.8 Hz, 1H), 6.93 - 6.77 (m, 1H), 5.23 (d, J = 10.0 Hz, 1H), 4.63 (t, J = 9.2 Hz, 1H), 4.09 (dd, J = 2.2, 5.0 Hz, 1H), 2.67 - 2.61 (m, 1H), 1.67 (s, 3H), 0.69 (d, J = 6.4 Hz, 3H); m / z (ESI): [M + H]+ = 500.2. Example 55 F Br—|—Br F                                  F                                    F                                              p TBS^^ -----55:2---->■ TBS ~—^Br ---------»- TBS^=—4-F   -----------TBS^=—(-F F                        OH                        V0Tf 55-1                                       52-1                                   55.3                                            55.4 Example 55 Preparation of compound 52-1 Under a nitrogen atmosphere, a solution of n-butyllithium in n-hexane (33 mL, 82.50 mmol) was slowly added dropwise to a solution of compound 55-1 (13.3 mL, 71.28 mmol) in THF (80 mL) at -70°C. The mixture was stirred for 1 hour, and then compound 55-2 (23 g, 109.62 mmol) was slowly added dropwise to the reaction system. The mixture was allowed to warm to 20°C and stirred for another 15 hours. The reaction solution was poured into ice-cold aqueous ammonium chloride solution (100 mL), and the mixture was extracted with petroleum ether (200 mL x2). The organic phases were combined, and then washed once with water and once with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation to obtain a crude product. The crude product was dissolved in 50 ml of petroleum ether, and filtered through a pad of silica gel (10 cm thick). The filtrate was concentrated to dryness to obtain compound 52-1. Preparation of compound 55-3 Compound 52-1 (10 g, 37.15 mmol) was dissolved in tetrahydrofuran (10 mL) and water (40 mL). Indium powder (6 g, 52.26 mmol) was added, and the mixture was subjected to ultrasonic vibration for 8 hours. Aqueous formaldehyde solution (16 g, 197.14 mmol) was added to the reaction solution, and the mixture was stirred for another 32 hours. The reaction solution was diluted with ethyl acetate (300 mL) and filtered, and the filtrate was allowed to stand for liquid separation. The upper ethyl acetate phase was separated and washed once with saturated sodium chloride aqueous solution. The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation to obtain a crude product, which was purified by silica gel column chromatography to obtain compound 55-3. Preparation of compound 55-4 Compound 55-3 (500 mg, 2.27 mmol) and pyridine (0.5 mL, 6.18 mmol) were dissolved in DCM (10 mL). Trifluoromethanesulphonic anhydride (0.5 mL, 3.01 mmol) was slowly added in an ice bath, and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with ethyl acetate (200 mL), and washed sequentially with water (100 mL *2) and saturated sodium chloride aqueous solution (100 mL). The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation to obtain compound 55-4. Preparation of example 55 Compound 55-4 (130 mg, 0.37 mmol) and compound 1-18 (170 mg, 0.37 mmol) were dissolved in DMF (5 mL). Potassium carbonate (180 mg, 1.30 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The reaction solution was poured into water (100 mL), and the mixture was extracted with ethyl acetate (100 mL x2). The organic phase was dried over anhydrous sodium sulphate, filtered, and concentrated to dryness by rotary evaporation to obtain a crude product, which was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150*25 mm * 10 um); flow rate: 25 mL / min; gradient: 42% - 72% B over 15 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 55. m / z (ESI): [M + H]+ = 548.1. Examples 56 and 57 Preparation of compound 56-1 Under a nitrogen atmosphere, triethylamine (1.1 mL, 7.87 mmol) was added to a solution of 24-3 (314 mg, 0.79 mmol) in 3 mL of dichloromethane, followed by the addition of a solution of compound 22-5 (198.83 mg, 1.02 mmol) in 3 mL of DCM. The mixture was stirred at 26°C for 2 hours. After the reaction was completed, the reaction solution was quenched with 10 mL of water, and extracted with dichloromethane (10 mLx 3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 1 / 1) to obtain compound 56-1. Preparation of examples 56 and 57 Under a nitrogen atmosphere, trifluoroacetic acid (800.8 ill, 10.78 mmol) was added to a solution of compound 56-1 (300 mg, 0.54 mmol) in 9 mL of dichloromethane. The reaction solution was reacted at 25°C for 2 hours. After the reaction was completed, the reaction solution was concentrated to obtain a crude product, which was purified by reversed-phase preparative chromatography (Waters Xbridge 150 x 25 mm x 5 um, water (water (NH4HCOs)-ACN, 38% - 68% over 12 min) to obtain a mixture of example 56 and example 57. The mixture was resolved by SFC (column: DAICEL CHIRALCEL OX (250 mm*30 mm, 10 um); mobile phase: [A: CO2;B: EtOH(0.1%NH3H2O)]; B%: 15.00%-15.00%, 60.00 min; flow rate: 150.00 g / min) to obtain two single isomers. Example 56 (retention time=1.497 minutes) 1H NMR (400 MHz, DMSO-d6): 6 10.36 (s, 1H), 8.71 - 8.56 (m, 1H), 8.09 - 7.88 (m, 1H), 7.50 - 7.37 (m, 1H), 7.29 - 7.08 (m, 2H), 5.44 - 5.29 (m, 1H), 5.16 - 5.04 (m, 1H), 4.70 - 4.60 (m, 1H), 4.57 - 4.48 (m, 1H), 4.40 - 4.26 (m, 1H), 3.70 - 3.57 (m, 2H), 3.49 - 3.39 (m, 1H), 2.91 - 2.75 (m, 1H), 1.61 (s, 3H), 0.81 - 0.63 (m, 3H); m / z (ESI): [M+ H]+ =517.3. Example 57 (retention time=1.655 minutes) 1H NMR (400 MHz, DMSO-d6): 5 10.37 (s, 1H), 8.72 - 8.59 (m, 1H), 7.97 (dd, J = 2.4, 8.6 Hz, 1H), 7.42 (d, J = 8.5 Hz, 1H), 7.29 - 7.10 (m, 2H), 5.34 (d, J = 4.8 Hz, 1H), 5.10 (d, J = 10.5 Hz, 1H), 4.64 (br t, J = 5.8 Hz, 1H), 4.59 - 4.47 (m, 1H), 4.31 (dd, J = 7.5, 10.3 Hz, 1H), 3.71 - 3.57 (m, 2H), 3.44 (td, J = 5.9, 11.4 Hz, 1H), 2.83 (t, J = 7.3 Hz, 1H), 1.61 (s, 3H), 0.74 (d, J = 6.0 Hz, 3H); m / z: [M+ H]+ = 517.1. Examples 58 and 59 Preparation of compound 58-1 To a solution of compound 50-1 (500 mg, 1.47 mmol) in DCM (5 mL) were added DMF (10 mg, 0.15 mmol) and oxalyl chloride (0.4 mL, 4.41 mmol). The mixture was stirred at 25°C for 1 hour. The mixture was concentrated. Under a nitrogen atmosphere, triethylamine (0.6 mL, 4.35 mmol) and the resulting concentrate were sequentially added to a solution of compound 56-5 (337.89 mg, 1.74 mmol) in 10 mL of dichloromethane, and the reaction solution was stirred at 26°C for 16 hours. After the reaction was completed, the mixture was diluted with 30 mL of water, and extracted with ethyl acetate (30 mL *2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - 1 / 1) to obtain compound 58-1. 1H NMR (400 MHz, CDCl3): 5 = 8.56 (d, J = 2.4 Hz, 1H), 8.41 (s, 1H), 8.13 (dd, J = 2.4, 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.09 (t, J = 6.8 Hz, 1H), 6.83 -6.72 (m, 1H), 6.31 (s, 1H), 5.18 (t, J = 6.8 Hz, 1H), 5.14 - 5.03 (m, 1H), 4.44 (t, J = 7.6 Hz, 1H), 3.91 (t, J = 7.6 Hz, 1H), 2.92 - 2.79 (m, 1H), 1.70 (s, 3H), 1.51 (d, J = 14.4 Hz, 6H), 0.87 - 0.78 (m, 3H); m / z (ESI): [M+ H]+ =517.2. Preparation of compound 58-2 Under a nitrogen atmosphere, trifluoromethanesulphonic anhydride (83.5 uL, 0.50 mmol) was added to a solution of compound 58-1 (280 mg, 0.61 mmol) in 4 mL of dichloromethane at 0°C. The reaction solution was stirred at 0°C for 2 hours. After the reaction was completed, the reaction solution was quenched with 20 mL of water, and extracted with dichloromethane (30 mL x2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - 2 / 1) to obtain compound 58-2. Preparation of compound 58-3 Under a nitrogen atmosphere, ethynyl[tris(propan-2-yl)]silane (0.2 mL, 0.77 mmol), cuprous iodide (3.0 mg, 0.02 mmol), triethylamine (23.4 mg, 0.23 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (8.46 mg, 0.01 mmol) were sequentially added to a solution of compound 58-2 (50 mg, 0.08 mmol) in 1.5 mL of N,N-dimethylformamide. The reaction solution was warmed to 100°C and stirred for 16 hours. After the reaction was completed, the mixture was cooled to room temperature, diluted with 20 mL of water and 20 mL of ethyl acetate, and filtered. The filtrate was extracted with ethyl acetate (10 mLx2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by preparative silica gel thin-layer chromatography (petroleum ether / ethyl acetate=3 / 1) to obtain compound 58-3. Preparation of compound 58-4 Under a nitrogen atmosphere, trifluoroacetic acid (262 uL, 3.53 mmol) was added to a solution of compound 58-3 (120 mg, 0.18 mmol) in 2 mL of dichloromethane. The reaction solution was stirred at 25°C for 0.5 hours. After the reaction was completed, the reaction solution was adjusted to pH 7 by slow dropwise addition of saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane (20 mL x2). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated under reduced pressure to obtain compound 58-4. Preparation of examples 58 and 59 Under a nitrogen atmosphere, caesium fluoride (284 mg, 1.87 mmol) was added to a solution of compound 58-4 (120 mg, 0.19 mmol) in 2 mL of N,N-dimethylformamide. The reaction solution was stirred at 25°C for 0.5 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was purified by reversed-phase preparative chromatography (0.1% FA / ACN, 55%-65% over 5 min) to obtain a mixture of example 58 and example 59. The mixture was resolved by SFC (column: DAICEL CHIRALCEL OX (250 mm*30 mm, 10 um); mobile phase: [A: CO2;B: EtOH(0.1%NH3H2O)]; B%: 20.00%-20.00%, 4.00 min; flow rate: 150.00 g / min) to obtain two single isomers: Example 58 (retention time=1.587 minutes) 1H NMR (400 MHz, DMSO-d6): 3 10.39 (s, 1H), 8.64 (d, J = 2.4 Hz, 1H), 7.99 (dd, J = 2.4, 8.6 Hz, 1H), 7.61 - 7.50 (m, 1H), 7.42 (d, J = 8.6 Hz, 1H), 7.30 (dd, J = 4.4, 8.4 Hz, 1H), 5.34 (d, J = 4.8 Hz, 1H), 5.18 (d, J = 10.0 Hz, 1H), 5.03 (s, 1H), 4.64 (t, J = 6.0 Hz, 1H), 4.53 (td, J = 4.0, 6.8 Hz, 1H), 4.38 (dd, J = 7.8, 10.0 Hz, 1H), 3.68 - 3.58 (m, 1H), 3.43 (td, J = 6.0, 11.6 Hz, 1H), 2.97 - 2.84 (m, 1H), 1.60 (s, 3H), 0.73 (br d, J = 6.0 Hz, 3H); m / z (ESI): [M+ H]+ = 485.2. Example 59 (retention time=1.726 minutes) 1H NMR (400 MHz, DMSO-d6): 3 10.45 (s, 1H), 8.70 - 8.65 (m, 1H), 8.02 -7.95 (m, 1H), 7.61 - 7.49 (m, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.32 (dd, J = 4.4, 8.4 Hz, 1H), 5.35 (d, J = 4.8 Hz, 1H), 5.20 (d, J = 10.0 Hz, 1H), 5.02 (s, 1H), 4.65 (t, J = 6.0 Hz, 1H), 4.58 - 4.49 (m, 1H), 4.39 (dd, J = 7.8, 9.8 Hz, 1H), 3.68 - 3.59 (m, 1H), 3.48 - 3.41 (m, 1H), 2.96 - 2.82 (m, 1H), 1.60 (s, 3H), 0.73 (br d, J = 6.0 Hz, 3H); m / z: [M+ H]+ = 485.1. Example 60 Example 60 Preparation of compound 60-2 Under a nitrogen atmosphere, a solution of compound 60-1 (0.64 g, 5.60 mmol) in acetonitrile was added dropwise to a solution of cuprous iodide (0.1 g, 0.51 mmol) and ethynyltrimethylsilane (0.7 mL, 5.09 mmol) in acetonitrile (5 mL). The reaction solution was reacted at 25°C for 16 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 60-2. Preparation of compound 60-3 Under a nitrogen atmosphere, deuterated lithium aluminium hydride (0.13 g, 3.04 mmol) was slowly added portionwise to a solution of compound 60-2 (0.7 g, 3.80 mmol) in 20 mL of THF at 0°C. The reaction solution was reacted at 0°C for 1 hour. After the reaction was completed, the reaction solution was quenched by slow dropwise addition of 1.5 mL of deuterium oxide at 0°C, stirred for 10 minutes, and then warmed to 26°C. The mixture was dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain compound 60-3. Preparation of compound 60-4 Under a nitrogen atmosphere, cyanomethylenetributylphosphorane (210.17 mg, 0.87 mmol) was added to a solution of compound 1-18 (80 mg, 0.17 mmol) and compound 60-3 (170 mg, 1.39 mmol) in 2 mL of dioxane. The reaction solution was warmed to 40°C and stirred for 16 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with 10 mL of water, and extracted with ethyl acetate (5 mL*3). The combined organic phases were washed with 10 mL of saturated sodium chloride solution, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1-1 / 1) to obtain compound 60-4. Preparation of example 60 Under a nitrogen atmosphere, a solution of tetrabutylammonium fluoride in tetrahydrofuran (0.17 mL, 0.17 mmol) was added to a solution of compound 60-4 (50 mg, 0.09 mmol) in 1 mL of THF. The reaction solution was reacted at 25°C for 1 hour. After the reaction was completed, the reaction solution was quenched with 10 mL of water-, and extracted with ethyl acetate (5 mLx3). The combined organic phases were dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated to obtain a crude product, which was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150x25 mm x 10 um); flow rate: 25 mL / min; gradient: 42% - 72% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 60. 1H NMR (400 MHz, DMSO-d6): 5 10.81 - 10.60 (m, 1H), 8.55 - 8.46 (m, 1H), 8.33 - 8.26 (m, 1H), 8.11 - 8.01 (m, 1H), 7.90 - 7.80 (m, 1H), 7.69 - 7.58 (m, 1H), 7.27 - 7.07 (m, 2H), 5.19 - 5.05 (m, 1H), 4.44 - 4.26 (m, 1H), 2.92 - 2.79 (m, 2H), 2.70 - 2.60 (m, 2H), 1.72 - 1.57 (m, 3H), 0.79 - 0.64 (m, 3H); m / z (ESI): [M + H]+ = 514.0. Example 61 50-5                        61-1                         61-2                             61-3                       EXJUllplC 61 preparation of compound 61-1 Iodine (396.70 mg, 2.45 mmol) and aqueous ammonia (2.5 mL, 30% content) were added to a solution of compound 50-5 (500 mg, 1.22 mmol) in tetrahydrofuran (5 mL). The reaction solution was stirred at 30°C for 10 hours. The reaction solution was quenched with 30 mL of water and extracted with ethyl acetate (30 mL x 2). The combined organic phases were washed sequentially with saturated aqueous sodium sulphite solution (30 mL x 2) and saturated aqueous sodium chloride solution (30 mL x 1), dried over anhydrous sodium sulphate, filtered, and concentrated. The resulting crude product was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 10 : 1) to obtain compound 61-1. 1H NMR (400 MHz, CDCI3): S = 7.45 (q, J = 9.0 Hz, 1H), 7.24 (dd, J = 4.3, 8.8 Hz, 1H), 4.82 (d, J = 9.2 Hz, 1H), 4.15 - 4.12 (m, 1H), 2.94 - 2.89 (m, 1H), 1.66 (s, 3H), 1.39 (s, 9H), 0.88 - 0.79 (m, 3H). preparation of compound 61-2 Trifluoroacetic acid (2.00 mL) was added to a solution of compound 61-1 (300 mg, 0.74 mmol) in DCM (10 mL), and the mixture was stirred at 20°C for 5 hours. After the reaction was completed, the reaction solution was directly concentrated under reduced pressure to obtain compound 61-2. m / z (ESI): [M-H]- = 348.0. Preparation of compound 61-3 Compound 61-2    (260 mg, 0.74 mmol) and methyl 4-aminopyridine-2-carboxylate (169.90 mg, 1.12 mmol) were dissolved in acetonitrile      (5      mL).      Chloro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate (313.31 mg, 1.12 mmol) was added, and the mixture was reacted at 20°C for 16 hours. 30 mL of water was added to the reaction solution, and the mixture was extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate, filtered, and concentrated. The resulting crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3 / 7) to obtain compound 61-3. m / z (ESI): [M + H]+ = 484.2. Preparation of example 61 Compound 61-3 (100 mg, 0.21 mmol) was added to an ammonia solution in methanol (2 mL, 6 M), and the mixture was reacted at 20°C for 16 hours. After the reaction was completed, the reaction solution was directly concentrated under reduced pressure. The resulting crude product was purified by reversed-phase preparative chromatography ((Phenomenex luna C18 150x25 mm x 10 um); flow rate: 25 mL / min; gradient: 42% - 62% B over 10 min; mobile phase A: 0.225% aqueous methanoic acid, mobile phase B: acetonitrile) to obtain example 61. 1H NMR (400 MHz, DMSO-d6): S 10.68 (s, 1H), 8.50 (d, J = 5.6 Hz, 1H), 8.30 (d, J = 2.0 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.95 - 7.87 (m, 1H), 7.85 (dd, J = 2.0, 5.6 Hz, 1H), 7.62 (br s, 1H), 7.49 (dd, J = 4.4, 8.8 Hz, 1H), 5.26 (d, J = 9.2 Hz, 1H), 4.31 (t, J = 8.8 Hz, 1H), 2.91 (t, J = 7.6 Hz, 1H), 1.62 (s, 3H), 0.79 (d, J = 6.4 Hz, 3H); m / z (ESI): [M + H]+ = 469.0. Experimental example 1 Measurement of inhibitory activity of compounds of the present invention against voltage-gated sodium channel NaV1.8 by manual patch clamp method Cell culture and passage: CHO cells stably expressing human NaV1.8 were cultured in a Ham’s F-12 medium containing 10% foetal bovine serum, 10 iigmL Blasticidin, 200 gg / mL Hygromycin B, and 100 gg / mL Zeocin. The cells were cultured at 37°C with a carbon dioxide concentration of 5%. During cell passage, the old medium was removed, and the cells were washed once with PBS. Then, 0.25%-Trypsin-EDTA solution was added, and the cells were incubated at 37°C. Once the cells detached from the bottom of the dish, an appropriate amount of complete medium pre-warmed to 37°C was added. The cells were dispersed from the bottom of the dish and then transferred to a sterile centrifuge tube. The tube was centrifuged at 1000 rpm for 5 min to collect the cells, which were then seeded into 6 cm cell culture dishes (2.5 x 105 cells / dish in 5 mL of medium) for expansion or maintenance. To maintain the electrophysiological activity of the cells, the cell density should not be lower than 80%. Before patch clamp testing, CHO cells stably expressing human NaV1.8 were dissociated with 0.25% Trypsin-EDTA solution and counted. 6.5 x 103 cells were plated onto coverslips and cultured in a 24-well plate (final volume: 500 pL) for 18 hours before measurements. Compound sample preparation: Test compounds were dissolved in dimethyl sulphoxide (DMSO) to prepare 100 mM stock solutions, which were then diluted with extracellular solution containing 100 nM tetrodotoxin (TTX) (140 mM NaCl, 3.5 mM KCl, 1 mM MgCb^O, 2 mM CaCh^O, 10 mM D-Glucose, 10 mM HEPES, 1.25 mM NaH2PO4<H2O, adjusted to pH=7.4 with NaOH) to obtain working solutions at various concentrations. The DMSO concentration in each working solution was 0.1%. Prior to measurements, the working solutions of the test compound were sonicated for 20 min. Patch clamp measurement: For patch clamp operation, capillary glass tubes were first pulled into recording electrodes using a microelectrode puller. Then, electrodes filled with an intracellular fluid (50 mM CsCl, 10 mM NaCl, 10 mM HEPES, 60 mM CsF, and 20 mM EGTA; adjusted to pH = 7.2 with CsOH) were installed into a microelectrode holder. Under an inverted microscope, a microelectrode manipulator was manipulated to bring a recording electrode into contact with the cell, and negative pressure suction was applied to form a GQ seal. At this point, fast capacitance compensation was performed, and then a negative pressure was continuously applied to rupture the cell membrane, establishing a whole-cell recording mode. Finally, slow capacitance compensation was performed, and relevant parameters were recorded. No electric leakage compensation was provided. When the sodium current in whole-cell recording was stable, drug administration was initiated. Each drug concentration was allowed to act 5 min (or until the current was stable) before the next concentration was tested. Coverslips plated with cells were placed in a recording chamber under an inverted microscope. The blank control extracellular solution and the test compound working solution were sequentially perfused through the recording chamber from low concentration to high concentration via a gravity-driven perfusion method, thereby acting on the cells. A peristaltic pump was used for liquid exchange during recording. For each cell, the current detected in the compound-free extracellular solution was used as its own control group. Each concentration was independently tested in duplicate. All electrophysiological experiments were conducted at room temperature. Specifically, each test compound was tested at 2 concentrations (for initial screening) or 5 concentrations (for IC50 determination). The inhibitory activity of test compounds against NaV1.8 sodium channels was determined by calculating the relative percentage of the peak current of cells treated with the test compound versus the peak current of the control group. The voltage stimulation protocol for whole-cell patch clamp recording of NaV1.8 sodium currents: After establishment of the whole-cell seal, the cells were voltage-clamped at -120 mV. The voltage was first stepped from -130 mV to -10 mV in 10 mV increments and maintained for 5 s, followed by the application of a depolarising pulse to 0 mV to obtain a half-inactivation voltage (Vhalf). The resting state and half-inactivated state of sodium currents were measured using a dual-pulse mode. A first depolarising pulse (TP1) to 0 mV for 50 ms was applied to measure the sodium current in the resting state. Subsequently, the voltage was adjusted to Vhalf and maintained for 5 s. The voltage was then returned to -120 mV for 20 ms, followed by a second depolarising pulse (TP2) to 0 mV for 50 ms was then applied to measure the sodium current in the half-inactivated state. Finally, the voltage was 5 returned to the clamping voltage of -120 mV. Data were acquired every 20 ms to monitor the effects of the drugs on peak sodium currents in the two different states. The inhibitory activities of example compounds against NaV1.8 channels were determined using the above assay. The inhibition rates at 1 nM and IC50 measured are shown in Tables 1 and 2. 10      Table 1. Inhibitory activities (inhibition rates) of example compounds against NaV1.8 channels Example Inhibition rate at 1 nM / % Resting state Half-inactivated state 1 97.03 97.53 2 97.41 96.79 3 63.16 62.49 5 99.25 99.92 15 91.57 89.51 16 89.55 89.07 17 91.12 92.09 18 98.24 97.76 19 94.69 94.96 20 96.75 95.88 24 92.26 93.60 25 84.00 88.38 29 96.35 97.29 30 92.95 93.06 31 88.10 87.43 32 99.25 99.92 39 96.35 97.29 40 88.04 85.84 41 91.61 89.62 44 87.91 85.75 45 87.44 90.25 46 86.07 81.93 48 96.31 96.63 51 88.34 90.09 55 85.07 81.21 Table 2. Inhibitory activities (IC50) of example compounds against NaV1.8 channels Example IC50 / nM Resting state Half-inactivated state 1 0.022 0.027 12 0.019 0.029 24 0.033 0.048 61 0.78 0.89 The experimental results showed that the example compounds of the present invention all exhibited good inhibitory effects against NaV1.8 channels. 5       Experimental example 2: In vivo pharmacokinetic study in rats following single intravenous injection or oral gavage administration. Experimental methods: Six male SD rats weighing 200-300 g were divided into two groups: one group received a single oral dose of 5 mg / kg, and the other group received a single dose of 1 mg / kg via tail vein. The animals in the oral group were 10 fasted overnight and allowed free access to food 4 hours post-administration, whereas the animals in the intravenous group had free access to food. Blood samples were collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h post-administration. After pre-treatment, the plasma samples were detected by LC / MS / MS in MRM mode, and an appropriate standard curve was established to quantify the target compound in 15 the plasma samples, thereby obtaining the drug concentration-time curve. Pharmacokinetic parameters were calculated using a non-compartmental model in WinNonlin software. The experimental results are as shown in the table below. Table 3. Pharmacokinetic parameters of example compounds of the present invention in rats Rat PK parameter Example 3 Example 12 Example 24 Example 61 Administration dose (mg / kg) 1 1 1 1 Intravenous injection Clearance CL (mL / min / kg) 5.19 8.9 24.1 3.97 Apparent volume of distribution Vss (L / kg) 1.13 1.26 1.06 1.53 Exposure AUCo-last (h*ng / mL) 3032 1858 707 4494 Half-life T1 / 2 (h) 3.51 2.17 0.771 5.32 Oral administration Administration dose (mg / kg) 5 5 30 5 Maximum plasma concentration Cmax (ng / mL) 696 718 5023 1181 Time to peak concentration Tmax (h) 4.67 6 7.33 6.67 Exposure AUCo-last (h*ng / mL) 8920 9600 69366 17898 Half-life T1 / 2 (h) 4.46 2.81 2.4 6.24 Oral bioavailability F(%) 56 98 - 83 The experimental results showed that the example compounds of the present invention exhibited high plasma concentrations, high exposure, and low clearance in rats, demonstrating significant pharmacokinetic advantages. Experimental example 3: In vivo pharmacokinetic study in mice following 5 single intravenous injection or oral gavage administration. Experimental methods: Six male C57BL / 6 mice weighing 20-30 g were divided into two groups: one group received a single dose of 5 mg / kg via tail vein, and the other group received a single oral dose of 1 mg / kg. Both groups had free access to food. Blood samples were collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h post- 10 administration. After pre-treatment, the plasma samples were detected by LC / MS / MS in MRM mode, and an appropriate standard curve was established to quantify the target compound in the plasma samples, thereby obtaining the drug concentration-time curve. Pharmacokinetic parameters were calculated using a non-compartmental model in WinNonlin software. The experimental results are as shown in the table below. Table 4. Pharmacokinetic parameters of example compounds of the present invention in mice Mouse PK parameter Example 3 Example 12 Example 24 Example 61 Intravenous injection Administration dose (mg / kg) 1 1 1 1 Clearance CL (mL / min / kg) 3.35 14.8 18.7 5.84 Apparent volume of distribution Vss (L / kg) 0.892 1.22 1.07 1.75 Exposure AUCo-last (h*ng / mL) 4998 1129 904 2807 Half-life T1 / 2 (h) 2.33 1.22 0.89 4.62 Oral administration Administration dose (mg / kg) 30 30 30 30 Maximum plasma concentration Cmax (ng / mL) 5145 5590 9563 5520 Time to peak concentration Tmax (h) 1.25 2 2 1.67 Exposure AUCo-last (h*ng / mL) 76666 71639 84854 53267 Half-life T1 / 2 (h) 10.2 2.17 3.1 4.26 5        The experimental results showed that the example compounds of the present invention exhibited high plasma concentrations and high exposure in mice, demonstrating pharmacokinetic advantages. Experimental example 4: In vivo pharmacokinetic study in dogs following single intravenous injection or oral gavage administration. 10        Experimental methods: Six male beagle dogs weighing 9-11 kg were divided into two groups: one group received a single dose of 0.5 mg / kg via tail vein, and the other group received a single oral dose of 1 mg / kg. The animals in the intravenous group had free access to food, whereas the animals in the oral group were fasted overnight and allowed to free access to food 4 hours post-administration. Blood samples were collected from the intravenous group at 0.083, 0.25, 0.5, 1, 2, 4, 8, 24, and 48 h post-administration, and from the oral group at 0.25, 0.5, 1, 2, 4, 8, 24, 32, 5 and 48 h post-administration. After pre-treatment, the plasma samples were detected by LC / MS / MS in MRM mode, and an appropriate standard curve was established to quantify the target compound in the plasma samples, thereby obtaining the drug concentration-time curve. Pharmacokinetic parameters were calculated using a non-compartmental model in WinNonlin software. The experimental results are as 10 shown in the table below. Table 5. Pharmacokinetic parameters of example compounds of the present invention in dogs Dog PK parameter Example 3 Example 12 Example 24 Intravenous injection Administration dose (mg / kg) 0.5 0.5 0.5 Clearance CL (mL / min / kg) 0.202 1.96 1.61 Apparent volume of distribution Vss (L / kg) 0.835 0.866 0.587 Exposure AUC0-last (h*ng / mL) 21416 4612 5171 Half-life T1 / 2 (h) 48.3 6.37 4.34 Oral administration Administration dose (mg / kg) 1 1 1 Maximum plasma concentration Cmax (ng / mL) 1126 490 721 Time to peak concentration Tmax (h) 2 2 2 Exposure AUC0-last (h*ng / mL) 42706 8650 9695 Half-life T1 / 2 (h) 101 8.5 4.7 Oral bioavailability F(%) >100 95.4 92.0 The experimental results showed that the example compounds of the present invention exhibited low clearance, high exposure, and high oral bioavailability in dogs, demonstrating pharmacokinetic advantages. Experimental example 5: In vivo pharmacokinetic study in monkeys following single intravenous injection or oral gavage administration. Six male cynomolgus monkeys weighing 3.0-3.3 kg were divided into two groups: one group received a single intravenous dose of 1 mg / kg, and the other group received a single oral dose of 2 mg / kg. The animals in the intravenous group had free access to food, whereas the animals in the oral group were fasted overnight and allowed to free access to food 4 hours post-administration. Blood samples were collected from the intravenous group at 0.083, 0.25, 0.5, 1, 2, 4, 8, 24, and 48 h postadministration, and from the oral group at 0.25, 0.5, 1, 2, 4, 8, 24, 32, and 48 h postadministration. After pre-treatment, the plasma samples were detected by LC / MS / MS in MRM mode, and an appropriate standard curve was established to quantify the target compound in the plasma samples, thereby obtaining the drug concentration-time curve. Pharmacokinetic parameters were calculated using a non-compartmental model in WinNonlin software. The experimental results are as shown in the table below. Table 6. Pharmacokinetic parameters of example compounds of the present invention in monkeys Monkey PK parameter Example 24 Example 61 Intravenous injection Administration dose (mg / kg) 1 1 Clearance CL (mL / min / kg) 8.88 5.45 Apparent volume of distribution Vss (L / kg) 1.50 1.74 Exposure AUC0-last (h*ng / mL) 1876 3128 Half-life T1 / 2 (h) 2.98 6.10 Administration dose (mg / kg) 2 2 Oral administration Maximum plasma concentration Cmax (ng / mL) 279 307 Time to peak concentration Tmax (h) 3.33 4.00 Exposure AUCo-last (h*ng / mL) 2364 3717 Half-life Ti / 2 (h) 3.57 5.21 Oral bioavailability F(%) 63.6 59.4 The experimental results showed that the example compounds of the present invention exhibited low clearance, high exposure, and high oral bioavailability in dogs, demonstrating pharmacokinetic advantages. Experimental example 6: Solubility of compounds of the present invention. Experimental methods: A 15 pL of a 10 mM DMSO stock solution was added to 96-well plates containing 485 pL of phosphate buffer (PBS pH 7.4), fasted-state simulated intestinal fluid (FaSSIF pH 6.5), fed-state simulated intestinal fluid (FeSSIF pH 5.0), and fasted-state simulated gastric fluid (FaSSGF pH 1.6) (n=2), respectively. The final concentration was 300 pM (containing 3% DMSO). A stir bar was added to each well, and then the plates were sealed and shaken in a thermomixer at 25°C and 1100 rpm for 2 h. Upon completion of the shaking, the samples were filtered through a filter plate using a vacuum manifold. 5 pL of the filtrate was mixed with 5 pL of DMSO, and the mixture was diluted by the corresponding fold with an appropriate volume of a mixed solution of ultrapure water and acetonitrile (1:1) containing an internal standard. After thorough mixing, the resultant was subjected to LC-MS / MS injection and analysis. 5 pL of the 300 pM DMSO standard solution was mixed with 5 pL of the respective buffer. The mixture was diluted by the corresponding fold with an appropriate volume of a mixed solution of ultrapure water and acetonitrile (1:1) containing an internal standard. After thorough mixing, the resultant was analysed by LC-MS / MS together with the samples. The experimental results are as shown in the table below. The solubility values of test samples and standard reference were calculated according to the following formula: I                                 Peak area of test sample x Dilution factor x Concentration of reference Concentration of test compound =-------------------------;-------—----------------------------- Peak area of reference Table 7. Solubility of compounds of the present invention Example Kinetic solubility (pM) in different systems FaSSIF FeSSIF FaSSGF Example 3 33.4 293 32 Example 12 49.22 300 10.54 Example 24 284 315 106 Example 61 19.89 72.33 48.32 The experimental results showed that the example compounds of the present invention exhibited good solubility in FaSSIF, FESSIF and FaSSGF solutions. Experimental example 7: CYP inhibition of compounds of the present 5 invention. Experimental methods: Specific probe substrates for CYP450 isozymes were incubated with human liver microsomes and various concentrations of the test compounds. The reaction was initiated by the addition of reduced nicotinamide adenine dinucleotide phosphate (NADPH). After the reaction was completed, the 10 samples were treated, and the concentrations of metabolites produced from the probe substrates were quantified by liquid chromatography-tandem mass spectrometry (LC-MS / MS). The IC50 values were then calculated. The experimental results are as shown in the table below. Table 8. Effects of example compounds of the present invention on human liver 15                        microsomal cytochrome P450 activity Exampl e Inhibitory activity IC50 / pM CYP 1A2 CYP2 B6 CYP2 C8 CYP2 C9 CYP2C 19 CYP2 D6 CYP3 A-M CYP3 A-T Exampl e 3 >30 28.4 9.2 12.7 6.25 12.6 >30 24.9 Exampl e 24 >30 >30 21.3 28.5 27 >30 24.7 16.4 Exampl e 61 >30 >30 11.6 7.3 15.8 >30 >30 20.0 The experimental results showed that the example compounds of the present invention exhibited weak inhibition against cytochrome P450 isozymes, indicating a low risk of drug-drug interactions. Experimental example 8: Metabolic stability of compounds of the present invention in liver microsomes. Experimental methods: In a 100 mM phosphate buffer system (pH 7.4), appropriate volumes of human, monkey, dog, rat, or mouse liver microsomes (final protein concentration: 0.5 mg / mL) and reduced nicotinamide adenine dinucleotide phosphate (NADPH, final concentration: 1 mM) were mixed and pre-incubated at 37°C with shaking for 10 min. An appropriate volume of the target compound (final concentration: 1 gM) was then added to initiate the reaction, with the organic solvent content not exceeding 1%. At 0.5, 5, 15, 30, and 60 min after the reaction, equal volumes of the incubation mixture were collected, and the reaction was terminated by adding an appropriate volume of ice-cold acetonitrile solution containing an internal standard. The samples were centrifuged at 3220 g for 40 min, and the supernatant was diluted with ultrapure water and subjected to quantitative analysis by LC-MS / MS. The peak area ratio of the target compound to the internal standard at 0.5 min was set as 100%, and the relative remaining percentages of the target compound at other time points were calculated. Linear regression analysis was performed on the natural logarithm of the remaining percentage of the target compound at each time point versus incubation time to obtain the slope (k). The half-life was calculated using the formula .t1 / 2 = -0.693 / k. The experimental results are as shown in the table below: Table 9. Metabolic stability of example compounds of the present invention in liver microsomes Example Metabolic half-life T1 / 2 (minute) across various species Human Monkey Dog Rat Mouse Example 3 >184 29 >184 73.4 58.9 Example 24 111 47.5 113 90 102 Example 61 176 26.8 >184 >184 >184 The experimental results showed that the example compounds of the present invention were relatively stable in liver microsomes of various species. Experimental example 9: Metabolic stability of compounds of the present invention in hepatocytes. Experimental methods: Human, monkey, dog, rat, or mouse hepatocytes (cell density: 0.5 x 106 cells / mL) were mixed with the target compound (final concentration: 1 pM) and incubated in an incubator at 37°C with shaking for 120 min, with the organic solvent content not exceeding 1%. At 0.5, 15, 30, 60, 90, and 120 min after the reaction, equal volumes of the incubation mixture were collected, and the reaction was terminated by adding an appropriate volume of ice-cold acetonitrile containing an internal standard. The samples were centrifuged at 3220 g for 45 min, and the supernatant was diluted with ultrapure water and subjected to quantitative analysis by LC-MS / MS. The peak area ratio of the target compound to the internal standard at 0.5 min was set as 100%, and the relative remaining percentages of the target compound at other time points were calculated. Linear regression analysis was performed on the natural logarithm of the remaining percentage of the target compound at each time point versus incubation time to obtain the slope (k). The half-life was calculated using the formula .t1 / 2 = -0.693 / k. The experimental results are as shown in the table below: Table 10. Metabolic stability of example compounds of the present invention in hepatocytes Example Metabolic half-life T1 / 2 (minute) across various species Human Monkey Dog Rat Mouse Example 3 107 96 ot 97 57 Example 24 463 121 286 72 77 Example 61 ot 91 >573 56 53 The experimental results showed that the example compounds of the present invention were relatively stable in hepatocytes of various species. Experimental example 10: Plasma protein binding rate of compounds of the present invention. Experimental methods: A 10 mM DMSO stock solution was diluted with DMSO to obtain a 1 mM working solution. 3 pL of the working solution of the test compound was added to 597 pL of pre-incubated plasma and mixed thoroughly. The final concentration of the test compound in plasma was 5 pM. The final organic solvent content in the incubation system was 0.5%. After mixing thoroughly, 50 pL of the incubation system was immediately transferred to a new 96-well plate as the zero-time sample, which was treated in the same manner as the post-incubation samples. After assembling the equilibrium dialysis plate and dialysis membrane, 120 pL of the plasma sample containing the test compound and 120 pL of phosphate buffer (pH 7.4) were added to the chambers separated by the dialysis membrane. The plate was sealed and incubated on a vortex mixer at 300 rpm for 6 h at 37°C in a 5% CO2 incubator. After the incubation was completed, the membrane was removed, and 50 pL of the sample was aspirated from each of the two chambers to a new 96-well plate. The remaining incubation system was incubated under the same conditions for the corresponding duration to assess the stability of the test compounds. After incubation, 50 pL of the incubation system was transferred and treated in the same manner as the plasma samples subjected to dialysis incubation. 50 pL of blank plasma was added to the harvested buffer sample. Similarly, an equal volume of blank buffer was added to the harvested plasma sample. After vortexing for 2 minutes, 400 pL of quenching solution (acetonitrile containing 0.5 pM tolbutamide) was added for protein precipitation. All samples were vortexed for 10 minutes and then centrifuged at 3000 g and 4°C for 30 minutes. 100 pL of the supernatant was transferred to a new 96-well plate and centrifuged again at 3000 g and 4°C for 30 minutes. 150 pL of the supernatant was transferred to a new 96-well plate, and mixed thoroughly with an equal volume of ultrapure water prior to LC-MS / MS analysis. All data were calculated by Microsoft Excel. Peak areas were determined from the extracted ion chromatograms. The percentages of free and bound fractions were calculated based on the peak area ratio of the test compound to the internal standard using the following formulas: Peak area ratio of test compound in buffer-side sample Free fraction (%)=---;--------:-----------------—---:------—------— X 100 Peak area ratio or test compound in plasma-side sample Bound fraction (%) = 100 - free fraction (%). The experimental results are as shown in the table below. Table 11. Plasma protein binding rate of compounds of the present invention Example Human plasma protein binding rate / % Example 24 97.38 Example 61 96.93 Experimental example 11: Pharmacodynamic study of example 3, 12 and 24 1.     Experiment objective To evaluate the analgesic effects of the compounds of the present disclosure, 5 male SD rats and male C57 BL / 6J mice were used to establish plantar incision pain models, and the changes in mechanical pain thresholds of the animals were measured. 2.     Experimental drugs example 3, example 12 and example 24. 5% DMSO, 10% solutol, and 85% saline were added sequentially, followed by vortexing until a clear solution was 10 obtained. 3.     Experimental materials and experimental methods 3.1 Species, strain, age, and sex of experimental animals SD rats, 6-8 weeks old, male; C57 BL / 6J mice, 6-8 weeks old, male. 3.2 Experimental animal grouping 15        After acclimatisation, the SD rats were divided into the following groups: Group Numb er of anima ls Administrat Adminis tration dose (mg / kg) Adminis ion Administr ation frequency Admini stration route tration volume (mL / kg) concentrati on (mg / mL) Vehicl e 8 / 5 / Single Gavage control Examp le 3 8 30 5 6 Single Gavage Examp le 12 8 15 5 3 Single Gavage Examp le 12 8 30 5 6 Single Gavage Examp le 24 8 30 5 6 Single Gavage After acclimatisation, the C57 BL / 6J mice were divided into the following groups: Group Numb er of anima ls Adminis tration dose (mg / kg) Adminis tration volume (mL / kg) Administrat ion concentrati on (mg / mL) Administr ation frequency Admini stration route Vehicl e control 8 / 10 / Single Gavage Examp le 3 8 60 10 6 Single Gavage Examp le 12 8 60 10 6 Single Gavage Examp le 24 8 30 10 3 Single Gavage Examp le 24 8 15 10 1.5 Single Gavage 3.3 Experimental methods Plantar incisional pain modelling: The experimental animals were anesthetised 5 and fixed on the surgical table in a prone position. The ipsilateral hind limb was extended with the plantar surface facing upward, secured with surgical tape, and disinfected. A longitudinal incision was made through the skin and fascia from the heel toward the toes on the plantar surface using a sterilised scalpel. One tip of a curved forcep was inserted beneath the lateral edge of the flexor digitorum brevis 10 muscle and pushed across to the medial side to elevate the muscle. A longitudinal incision was made through the muscle with the scalpel to ensure complete bisection of the muscle belly. The skin was sutured with 7-0 sutures and disinfected. The animals were returned to their housing cages and allowed to recover overnight after surgery. Oral gavage administration was performed, and the mechanical pain testing 15 was conducted 3 hours post-administration. Mechanical pain testing (Ascending method): The experimental animal was placed on a metal mesh stand for mechanical pain testing and allowed to acclimate for 30 min-60 min. Testing was initiated after the animal remained relatively calm without rearing or exploratory behaviour. Once the experimental animal was calm, a Von Frey filament was slowly and gently applied to the plantar surface of the hind limb to be tested, causing the filament to bend. The stimulus was maintained for 23 seconds, and paw withdrawal responses were observed. The filaments were applied to the test animal in ascending order of gram force (from the lowest to the highest gram force). Each filament strength was applied for five consecutive stimuli, with an inter-stimulus interval of at least 10 s. If fewer than three positive responses were observed, the next higher-force filament was used, and the above-described procedure was repeated. The first filament that induced three or more positive responses was recorded as the pain threshold for that animal (each animal was tested twice, and the average value was calculated). A response was marked as positive (x) if the experimental animal showed paw lifting, flinching, or licking in response to the stimulus; paw withdrawal responses caused by body movement were excluded; and a response was marked as negative (o) if none of the above behaviours were observed. Filament forces: rats: 0.6, 1.0, 1.4, 2.0, 4.0, 6.0, 8.0, 10.0, 15.0 (g), with a cut-off value of 15.0 g; mice: 0.16, 0.40, 0.60, 1.00, 1.40, 2.00 (g), with a cut-off value of 2.00 g. 3.4 Data analysis Data were summarised and statistically analysed using SPSS statistical software (version R26.0.0.0), and results were presented as means and standard errors. Graphs were generated using Graph Pad (version 8.0.2) based on the SPSS statistical results. One-way ANOVA and t-test were used for data assessment. Percentage increase in threshold (%) = [(Gt-Go) / Go] x 100 (%), where Gt represents the plantar pain threshold of the treatment group, and G0 represents the plantar pain threshold of the vehicle group. 4.     Results The analgesic efficacy of example 3, example 12, and example 24 in the rat plantar incision pain model is as shown in Table 12. The analgesic efficacy of example 3, example 12, and example 24 in the mouse plantar incision pain model is as shown in Table 13. Table 12. Analgesic efficacy of compounds of the present disclosure in rat plantar incision pain model Group Administra tion dose (mg / kg) Pain thresho ld (g) Percent age increase in threshol d (%) p (vs vehicle contro l) Administra tion route Num ber of anim als Vehicle control / 3.6±0.3 / / Gavage 8 Example 3 30 7.1±0.2 97.2 <0.000 1 Gavage 8 Example 12 15 7.0±0.3 94.4 <0.000 1 Gavage 8 Example 12 30 7.5±0.2 108.3 <0.000 1 Gavage 8 Example 24 30 8.1±0.3 125.0 <0.000 1 Gavage 8 5      Table 13. Analgesic efficacy of compounds of the present disclosure in mouse plantar incision pain model Percent Group Administra tion dose (mg / kg) Pain thresho ld (g) age increase in threshol d (%) p (vs vehicle control ) Administra tion route Num ber of anim als Vehicle control / 0.36±0. 02 / / Gavage 8 Example 3 60 0.70±0. 05 94.4 0.0031 Gavage 8 Example 12 60 0.78±0. 06 116.7 0.0002 Gavage 8 Example 24 30 0.74±0. 08 105.6 0.0009 Gavage 8 Example 24 0.54±0. 04 50.0 0.2468 Gavage 5. Conclusion Rat preoperative baseline pain threshold: Postoperatively, at 3 hours after administration, the pain threshold of the compound of example 3 at 30 mg / kg was 7.1 ± 0.2 g, representing a significant increase of 97.2% compared with the vehicle control group (p < 0.0001); the pain thresholds of the compound of example 12 at 15 mg / kg and 30 mg / kg were 7.0 ± 0.3 g and 7.5 ± 0.2 g, respectively, representing significant increases of 94.4% (p < 0.0001) and 108.3% (p < 0.0001) compared with the vehicle control group. The pain threshold of the compound of example 12 at 30 mg / kg was slightly higher than that at 15 mg / kg, indicating a near-saturated analgesic effect; the pain threshold of the compound of example 24 at 30 mg / kg was 8.1 ± 0.3 g, representing a significant increase of 125% compared with the vehicle control group (p < 0.0001), and its analgesic effect was significantly greater than that of example 3 compound at 30 mg / kg (p < 0.05). Mice preoperative baseline pain threshold: Postoperatively, at 3 hours after administration, the pain threshold of the compound of example 3 at 60 mg / kg was 0.70 ± 0.05 g, representing a significant increase of 94.4% compared with the vehicle control group (p < 0.01); the pain threshold of the compound of example 12 at 60 mg / kg was 0.78 ± 0.06 g, representing a significant increase of 116.7% compared with the vehicle control group (p < 0.001); the pain thresholds of the compound of example 24 at 30 mg / kg and 15 mg / kg were 0.74 ± 0.08 g and 0.54 ± 0.04 g, respectively, representing significant increases of 105.6% (p < 0.001) and 50.0% compared with the vehicle control group. The pain threshold of the compound of example 24 at 30 mg / kg was significantly higher than that at 15 mg / kg (p < 0.05), indicating a clear dose-dependent analgesic effect. Experimental example 12: Pharmacodynamic study of example 61 1.     Experiment objective To evaluate the efficacy of the compounds in a mouse plantar incisional pain model using the mechanical allodynia testing. 2.     Experimental drugs compound of example 61. 5% DMSO, 10% solutol, and 85% saline were added sequentially, followed by vortexing until a clear solution was obtained. 3.     Experimental materials and experimental methods 3.1 Species, strain, age, and sex of experimental animals: C57 BL / 6 mice, 6-8 weeks old, male. 3.2 Experimental animal grouping 5 After acclimatisation, the C57 BL / 6 mice were divided into the following groups: Group Numb er of anima ls Adminis tration dose (mg / kg) Administr ation volume (mL / kg) Administrat ion concentrati on (mg / mL) Administr ation frequency Admin istrati on route Naive control 10 / 10 / Single Gavag e Vehicle control 10 / 10 / Single Gavag e Exampl e 61 10 30 10 3 Single Gavag e Exampl e 61 10 60 10 6 Single Gavag e 3.3 Experimental methods Plantar incisional pain modelling: The animals were anesthetised with isoflurane, and the toe pinch reflex was assessed to confirm complete surgical 10 anaesthesia before surgery. Ophthalmic ointment was applied to the eyes to prevent corneal drying. The plantar surface of the left hind paw was disinfected three times with povidone-iodine and 70% ethanol, and the surgery was initiated after the skin had dried. A longitudinal incision about 5 mm in length was made starting 2 mm from the heel toward the toes. After the skin was incised, the flexor digitorum brevis 15 muscle was elevated and a longitudinal blunt injury was made to the muscle. The wound was sutured and disinfected. The animals were returned to their home cage after full recovery from anaesthesia (when they were able to move freely). Ten animals that did not undergo the incisional pain surgery served as the Naive control group. Mechanical allodynia testing (up-down method): One day after modelling, the mechanical allodynia testing was performed on the left hind paw of all model mice at 1, 3, and 6 hours post-administration. Each mouse was individually placed in Plexiglas chambers with mesh bottoms to allow access to the paws. The mice were allowed to acclimate for 15 minutes prior to testing. After acclimation, the centre of the plantar surface of the left hind paw was tested using the filaments. Eight filaments with the following bending forces were used: 2.36 (0.02 g), 2.44 (0.04 g), 2.83 (0.07 g), 3.22 (0.16 g), 3.61 (0.4 g), 3.84 (0.6 g), 4.08 (1 g), and 4.17 (1.4 g). During testing, each filament was applied perpendicularly to the skin surface with sufficient force to bend the filament for 6-8 seconds, with a 5-second interval between consecutive tests. Rapid paw withdrawal during filament application was recorded as a pain response. Paw withdrawal occurring as the filament was removed from the skin was also recorded as a pain response. If the animal moved or walked, no pain response was recorded, and the test was repeated. Testing began with the 3.22 (0.16 g) filament. If the animal showed a pain response, the next-lower-force filament was applied for the subsequent test; if no pain response was observed, the next higher-force filament was used in the following test. The highest filament force used in the tests was 4.17 (1.4 g). The test results were recorded in the table below: “X” denotes a pain response and “O” denotes no pain response. 2.36 2.44 2.83 3.22 o 3.61 o o o 3.84 x x x 4.08 4.17 Mechanical allodynia was expressed as the paw withdrawal threshold (PWT) in the mouse behavioural test and was calculated according to the following formula: 50% response threshold (g)= (10(XF+k5)) / 10,000 Xf = final filament value used in the test k = tabular value (refer to the literature: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994 Jul;53(1):55-63.) $ = mean difference 3.4 Data analysis Data were summarised and statistically analysed using Prism (Graph pad software, Inc.) software, and one-way ANOVA was used for data assessment. 4.     Results The analgesic efficacy of example 61 in the mouse plantar incision pain model is as shown in Table 14. Table 14. Analgesic efficacy of compounds of the present disclosure in mouse plantar incision pain model Group Adminis tration dose (mg / kg) 50% response threshold (g) Admin istrati on route Num ber of anim als 1 h 3 h 6 h Naive control / 1.28±0.05* *** 1.25±0.05* *** 1.15±0.05** ** Gavag e 10 Vehicle control / 0.32±0.02 0.32±0.04 0.32±0.04 Gavag e 10 Example 61 30 0.58±0.07* * 0.79±0.08* *** 0.60±0.08* Gavag e 10 Example 61 60 0.87±0.07* *** 1.07±0.09* *** 0.70±0.09** * Gavag e 10 Notes: Data are presented as Mean ± SEM; * vs. vehicle control, * P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. 5.     Conclusion The compound of example 61 exhibited significant analgesic efficacy in the mouse plantar incision pain model at different post-administration time points, with a clear dose-dependent effect. In the description of the present specification, references to the terms such as “an embodiment”, “some embodiments”, “examples”, “specific examples”, or “some examples” mean that specific features, structures, materials or characteristics described in combination with the embodiment(s) or example(s) are included in at least one embodiment or example of the present invention. In the present specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in any suitable manner. In addition, without any contradiction, a person skilled in the art may incorporate and combine different embodiments or examples and features of the different embodiments or examples described in the present specification. 5

Claims

1. A compound, characterised in that the compound is a compound asshown in formula (X), or a stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in formula (X),(X)whereinring A is phenyl, 5- to 10-membered heteroaryl or 5- to 10-membered heterocyclyl;each Re is independently H, D, F, Cl, Br, I, CN, hydroxyl, nitro, -N(Ra)2, -(C1-6 alkylene) N(Ra)2, -S(O)(=NH) C1-6 alkyl, -C(O)ORa, -C(O)N(Ra)2, -(C1-6N(Ra)2alkylene)C(O)N(Ra)2, -C(O)Ra, -S(O)2NRa,    N-Ra , alkyl, alkoxy, Cwhydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylthio, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkylene, C1-6 alkyl, c1-6 alkoxy, c1-6 hydroxyalkyl, c1-6 haloalkyl, c1-6 haloalkoxy, c1-6 alkylamino, c1-6 alkylthio, c3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, cl, Br, I, cN, hydroxyl, amino, nitro, oxo, hydroxyl, c1-3 alkyl, c1-3 alkylamino, c1-3 haloalkyl, c1-3 hydroxyalkyl and c1-3 alkoxy;each Ra is independently H, D, hydroxyl, c1-6 alkyl, c1-6 alkoxy, c3-6 cycloalkyl and 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, c1-6 alkoxy, c3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, cl, Br, I, cN, hydroxyl, amino, nitro, oxo and c1-3 alkyl;R1, R2, R3, R4 and R5 are each independently H, D, F, cl, Br, I, cN, hydroxyl, nitro, amino, c1-6 alkyl, c1-6 alkoxy, c1-6 alkylthio, c2-6 alkenyl, c2-6 alkynyl, c3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, c1-6 alkoxy, c1-6 alkylthio, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, nitro, amino, hydroxyl, C1-3 alkyl, C1-3 haloalkyl, C1-3 hydroxyalkyl and C1-3 alkoxy;or R3 and R5, together with the carbon atom to which they are attached, form C3-6 cycloalkyl;R6 is CN, -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, -CH=N-O-C1-6 alkyl, C2-6 alkynyl, C1-6 alkylthio or -L1-L2-Rc, wherein the C1-6 alkyl, C2-6 alkynyl and C1-6 alkylthio may be independently and optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, oxo and hydroxyl;L1 is a bond, O or S;L2 is a bond, C1-6 alkylene or -(C1-6 alkylene)-C1-6 alkoxy, wherein the C1-6 alkylene and C1-6 alkoxy may be independently and optionally substituted with 1 or 3 substituents selected from D, F, Cl, Br, I, oxo and hydroxyl;Rc is -O-N=, -P(O)(C1-6 alkyl)2, C2-6 alkynyl or -O-(3- to 8-membered heterocyclyl), wherein the C1-6 alkyl, C2-6 alkynyl and 3- to 8-membered heterocyclyl may be independently and optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from D, F, Cl, Br, I, hydroxyl, oxo, nitro, amino, alkylamino, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl;R7 and R8 are each independently H, D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, hydroxyl, amino, nitro and C1-3 alkoxy;n is 1, 2 or 3.

2. The compound according to claim 1, characterised in that ring A isphenyl, pyridazine, pyrazine, pyridine or pyrimidine.

3. The compound according to claim 1, characterised in that the compoundis a compound as shown in formula (I), (II) or (III), or a stereoisomer, geometricisomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in formula (I), (II) or (III),wherein(I),(II),(III)X is CR10 or N; Y is CR13 or N;R9 and R10 are each independently H, D, F, Cl, Br, I, CN, amino, nitro, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl or C1-6 haloalkoxy;R11, R12 and R13 are each independently H, D, F, Cl, Br, I, CN, hydroxyl, nitro, -N(Ra)2, -(C1-6 alkylene) N(Ra)2, -S(O)(=NH) C1-6 alkyl, -C(O)ORa, -C(O)N(Ra)2, -N(Ra)2(C1-6 alkylene)C(O)N(Ra)2, -C(O)Ra, -S(O)2NRa,    N-Ra , cw alkyl, C1-6 alkoxy,C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylthio, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkylene, C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylthio, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, oxo, hydroxyl, C1-3 alkyl, C1-3 alkylamino, C1-3 haloalkyl, C1-3 hydroxyalkyl and C1-3 alkoxy;each Ra is independently H, D, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein the C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl may be optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, oxo and C1-3 alkyl.

4. The compound according to any one of claims 1-3, characterised in thatR1, R2, R3, R4 and R5 are each independently H, D, F, Cl, Br, I, hydroxyl, methyl, ethyl, CH2F, CHF2, CF3, -CH2OCH3 or -CH2OH.

5. The compound according to any one of claims 1-4, characterised in thatR9, R10 and R11 are each independently H, D, F, Cl, Br, I, CN, amino, nitro, methyl, ethyl, methoxy, trifluoromethyl or trifluoromethoxy;R12 and R13 are each independently H, D, F, Cl, Br, I, CN, hydroxyl, amino, nitro, methyl, ethyl, CH2F, CHF2, -OCH3, -OCH2 CH3, -C(O)NH2, -C(O)NHOH, -C(O)NHOCH3, - CH2OH, -CH(OH)CH2OH, -C(O)NHCH3, -CH(OH)(CH3)2, -S(O)(=NH) CH3, -S(O)2NH2,nh2-¼N-OHor6.     The compound according to any one of claims 1-5, characterised in thatR7 and R8 are each independently H, D, F, Cl, Br, I, hydroxyl, methyl, ethyl, CH2F, CHF2 or CF3.

7. The compound according to any one of claims 1-6, characterised in thatR6 is CN, -S(O)C1-3 alkyl, -S(O)2C1-3 alkyl -CH=N-O-C1-3 alkyl, -C2-6 alkynyl, C1-3 alkylthio or -L1-L2-Rc, and the C1-3 alkyl, C1-3 alkylthio and C2-6 alkynyl may be independently and optionally substituted with 1, 2 or 3 substituents selected from D, F, Cl, Br, I, oxo and hydroxyl;L1 is a bond, O or S;L2 is a bond, C1-3 alkylene or -(C1-3 alkylene)- C1-3 alkoxy;Rc is -O-N=, -P(O)(CH3)2, C2-6 alkynyl or -O-(3- to 8-membered heterocyclyl), wherein the C2-6 alkynyl and 3- to 8-membered heterocyclyl may be independently and optionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from D, F, Cl, Br, I, hydroxyl, oxo, nitro, amino, C1-3 alkyl, C1-3 alkoxy, C1-3 alkylthio, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl.

8. The compound according to any one of claims 1-7, characterised in thatR6 is CN, -S(O)CH3, -S(O)2CH3,     :   ' 11, -P(O)(CH3)2,           ,            ,9.The compound according to claims1-8, characterised in that thecompound has a structure shown in formula (IV) or (V):10(IV)(V)wherein Rc is C2-6 alkynyl, and the C2-6 alkynyl may be independently andoptionally substituted with 1, 2, 3, 4, 5 or 6 substituents selected from D, F, Cl, Br, I, hydroxyl, nitro, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl.1510. A compound, characterised in that the compound is a compound having one of the following structures, or a stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug ofthe compound having one of the following structures:51013811. A pharmaceutical composition, characterised by comprising the compound according to any one of claims 1-10, wherein the pharmaceutical composition optionally further comprises a pharmaceutically acceptable excipient, carrier, adjuvant or any combination thereof.

512. Use of the compound according to any one of claims 1-10 or the pharmaceutical composition according to claim 11 in the preparation of a drug for treating a disease responsive to the inhibition of voltage-gated sodium channel NaV1.8.1013. The use according to claim 12, characterised in that the disease is chronic pain, enterodynia, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological 15 cough or arrhythmia.