WO2021174813A1 - Hydrogenated cyclic aza-, oxa- or hybrid aza/oxa-belt[n]aromatic hydrocarbon and preparation method therefor - Google Patents

Abstract

Disclosed are a hydrogenated cyclic aza-belt[n]aromatic hydrocarbon (formulae (I) and (II)), a hydrogenated cyclic oxa-belt[n]aromatic hydrocarbon (formulae (III) and (VI)) and a hydrogenated cyclic hybrid aza/oxa-belt[n]aromatic hydrocarbon (formulae (IV), (V) and (VII)) and a preparation method therefor.

Description

Aza, oxa, mixed nitrogen/oxa hydrogen ring zone [n] aromatic hydrocarbon and preparation method thereof

Priority information

This disclosure request was submitted to the State Intellectual Property Office of China on March 4, 2020. The patent application number is 202010142813.X, and the application name is "Aza, oxa, mixed nitrogen/oxahydrogen ring belt [n] aromatics and their The priority of the Chinese patent application of "Preparation Method", and the entire content of which is incorporated in the present disclosure by reference.

Technical field

The present disclosure relates to the field of organic chemistry. In particular, the present disclosure relates to aza, oxa, mixed nitrogen/oxa hydrogen ring zone [n] aromatics (n=8,12) and preparation methods thereof.

Background technique

Artificially synthesized macrocyclic compounds have the characteristics and advantages of good molecular structure designability and physical and chemical properties adjustable, and have been widely used in many fields of chemistry, materials science and life science. As the host compound, synthetic macrocyclic compounds can recognize anions, cations and neutral guest molecules, so that they can be used in separation, sensing and detection. As primitives or templates, functionalized macrocyclic compounds are used in the construction of functional assemblies and nanomaterials and molecular machines. Macrocyclic compounds also provide unique research methods and approaches for exploring chemical reaction mechanisms and supramolecular catalysis.

So far, a large number of artificially synthesized macrocyclic compounds have been reported in the literature, including crown ethers, globular ethers, chemically modified cyclodextrin derivatives, calixarene, calixorene, cyclotriveratrol, calixpyrrole, and cucurbita Urea, heterocalixarenes, cycloparaphenylenes (CPPs), pillared aromatics, crown aromatics, etc. are becoming dominant macrocyclic main molecules, and they have been studied in depth and extensively. Because different macrocyclic compounds have different structures, their cavity sizes, shapes, and electronic properties are different, thus showing different molecular recognition capabilities. Therefore, the macrocyclic compounds with new structures and functions still need to be studied in depth.

Public content

The present disclosure aims to solve one of the technical problems in the related art at least to a certain extent. For this reason, one purpose of the present disclosure is to propose azahydrogen ring belt [n] arene, oxahydrogen ring belt [n] arene, mixed nitrogen/oxahydrogen ring belt [n] arene (n=8,12) and其制造方法。 The method of preparation. This type of compound has the characteristics of barrel-shaped cavity structure, variable cavity volume size and adjustable cavity inner wall polarity, and has broad application prospects. For example, it can be used to selectively identify organic molecules from mixed solutions and form them. Inclusion complexes are applied to selective separation materials of small organic molecules, and can be applied to the preparation of organic photoelectric materials and other fields.

In one aspect of the present disclosure, the present disclosure proposes a compound. According to an embodiment of the present disclosure, the compound is a compound represented by formula (I) or a stereoisomer of a compound represented by formula (I),

in,

Ra is ^a hydrogen atom, optionally substituted C _1-12 alkyl, optionally substituted C _1-12 heteroalkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _5-24 cycloalkane Group, optionally substituted C _5-24 heterocyclyl or optionally substituted benzyl.

The compounds according to the above-mentioned embodiments of the present disclosure are also called "azahydrogen ring band [8] arene derivatives", which have a barrel-shaped cavity structure, a variable cavity volume size, and an adjustable cavity inner wall polarity. Features.

In addition, the compounds according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

In some embodiments of the present disclosure, Ra is ^a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 cycloalkyl, C _5-12 hetero Cycloalkyl, benzyl, or C _1-6 alkyl substituted benzyl.

In some embodiments of the present disclosure, Ra is ^a hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl Base, n-nonyl, n-decyl, benzyl, p-methylbenzyl, o-methylbenzyl, or m-methylbenzyl.

In some embodiments of the present disclosure, the compound has one of the following structures:

In another aspect of the present disclosure, the present disclosure proposes a compound. According to an embodiment of the present disclosure, the compound is a compound represented by formula (II) or a stereoisomer of a compound represented by formula (II),

in,

R ^b is a hydrogen atom, optionally substituted C _1-12 alkyl, optionally substituted C _1-12 heteroalkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _5-24 aryl , Optionally substituted C _5-24 heteroaryl, optionally substituted C _5-24 cycloalkyl, optionally substituted C _5-24 heterocyclyl or optionally substituted benzyl;

R ^1b is an optionally substituted C _5-24 aryl group, an optionally substituted C _5-24 heteroaryl group, an optionally substituted C _5-24 cycloalkyl group or an optionally substituted C _5-24 heterocyclic group.

The compounds according to the above-mentioned embodiments of the present disclosure are also called "azahydrogen ring band [8] arene derivatives", which have a barrel-shaped cavity structure, a variable cavity volume size, and an adjustable cavity inner wall polarity. Features.

In addition, the compounds according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

In some embodiments of the present disclosure, R ^b is a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 cycloalkyl, C _5-12 hetero Cycloalkyl, benzyl or C _1-6 alkyl substituted benzyl; R ^1b is C _1-6 alkyl substituted C _5-12 aryl, C _1-6 alkoxy substituted C _5-12 aryl Group, C _1-6 heteroalkyl substituted C _5-12 aryl, C _1-6 haloalkyl substituted C _5-12 aryl, C _5-12 cycloalkyl or C _5-12 heterocyclic group.

In some embodiments of the present disclosure, R ^b is a hydrogen atom, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n- Octyl, n-nonyl, n-decyl, benzyl, p-methylbenzyl, o-methylbenzyl or m-methylbenzyl; R ^1b is methyl, phenyl, p-methoxyphenyl, m-methyl Oxyphenyl, o-methoxyphenyl, 2,4-dimethoxyphenyl, 2,4,6-trimethoxyphenyl, p-methylphenyl, p-fluorophenyl, p-trifluoromethyl基phenyl.

In some embodiments of the present disclosure, the compound has one of the following structures:

In another aspect of the present disclosure, the present disclosure proposes a compound. According to an embodiment of the present disclosure, the compound is a compound represented by formula (III), a compound represented by formula (VI), a stereoisomer of a compound represented by formula (III), or a stereoisomer of a compound represented by formula (VI) body,

in,

R ^c is a hydrogen atom, optionally substituted C _1-12 alkyl, optionally substituted C _1-12 heteroalkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _5-24 cycloalkane Group, optionally substituted C _5-24 heterocyclyl or optionally substituted benzyl.

According to the compounds of the above-mentioned embodiments of the present disclosure, the compound represented by formula (III) is also called "oxahydrogen ring zone [8] arene derivatives", and the compound represented by formula (VI) is also called "oxahydrogen ring zone [12] Aromatic derivatives", this type of compound has the characteristics of a barrel-shaped cavity structure, a variable cavity volume and an adjustable polarity of the inner wall of the cavity.

In addition, the compounds according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

In some embodiments of the present disclosure, R ^c is a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 cycloalkyl, C _5-12 hetero Cycloalkyl, benzyl, or C _1-6 alkyl substituted benzyl.

In some embodiments of the present disclosure, R ^c is a hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl Base, n-nonyl, n-decyl, benzyl, p-methylbenzyl, o-methylbenzyl, or m-methylbenzyl.

In some embodiments of the present disclosure, the compound has one of the following structures:

In another aspect of the present disclosure, the present disclosure proposes a compound. According to the embodiments of the present disclosure, the compound is a compound represented by formula (IV), a compound represented by formula (V), a compound represented by formula (VII), a stereoisomer of a compound represented by formula (IV), and a compound represented by formula (V) ) The stereoisomer of the compound or the stereoisomer of the compound represented by formula (VII),

in,

R ^d , R ^1d , R ^2d and R ^3d are each independently a hydrogen atom, an optionally substituted C _1-12 alkyl group, an optionally substituted C _1-12 heteroalkyl group, and an optionally substituted C _2-12 alkene Group, optionally substituted C _5-24 aryl, optionally substituted C _5-24 heteroaryl, optionally substituted C _5-24 cycloalkyl, optionally substituted C _5-24 heterocyclyl or any Optional substituted benzyl.

Among the compounds according to the above-mentioned embodiments of the present disclosure, the compound represented by formula (IV) and the compound represented by formula (V) are also referred to as "mixed nitrogen/oxahydrogen ring band [8] arene derivatives", which are represented by formula (VII) The compounds shown are also called "mixed nitrogen/oxahydrogen ring belt [12] aromatic derivatives", which have the characteristics of barrel-shaped cavity structure, variable cavity volume size and adjustable cavity inner wall polarity.

In addition, the compounds according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

In some embodiments of the present disclosure, R ^d , R ^1d , R ^2d and R ^3d are each independently a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 aryl, C _1-6 alkyl substituted C _5-12 aryl, C _1-6 alkoxy substituted C _5-12 aryl, cyano substituted C _5-12 aryl, halogen substituted C _5-12 aryl, C _5-12 cycloalkyl, C _5-12 heterocycloalkyl, benzyl or C _1-6 alkyl substituted benzyl.

In some embodiments of the present disclosure, R ^d is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, N-nonyl, n-decyl; R ^1d , R ^2d , R ^3d are independently phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxybenzene Group, 4-cyanophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-tert-butylphenyl, 4-cumyl, 1-naphthyl, 2-naphthyl, benzyl.

In some embodiments of the present disclosure, the compound has one of the following structures:

In another aspect of the present disclosure, the present disclosure provides a method for preparing the compound represented by formula (I). According to an embodiment of the present disclosure, the method includes: subjecting a compound represented by formula (VIII) to an intramolecular Csp ² -N bond coupling reaction in the presence of a first transition metal catalyst to obtain a compound represented by formula (I),

Wherein, R ^a is as previously described.

According to the embodiments of the present disclosure, the compound represented by formula (VIII) undergoes an intramolecular Csp ² -N bond coupling reaction under the catalysis of transition metals to obtain the compound represented by formula (I) under mild reaction conditions and the resulting product is stable in the air It is easy to separate and purify, and has good practicability and application prospects.

In addition, the method for preparing the compound represented by formula (I) according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

According to an embodiment of the present disclosure, the above-mentioned first transition metal catalyst may include selected from the group consisting of palladium chloride, palladium acetate, tris(dibenzylideneacetone)dipalladium, tris(dibenzylideneacetone)dipalladium chloroform complex, tetrabenzene At least one of phosphonium palladium and ferrocene bis(diphenylphosphine) palladium chloride is preferably tris(dibenzylideneacetone)dipalladium. As a result, the reaction rate can be further increased, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -N bond coupling reaction is carried out under the action of a phosphine ligand and a base. The phosphine ligand may include selected from triphenylphosphine, tri-tert-butylphosphine, 1,1 '-Binaphthyl-2,2'-bisdiphenylphosphine, 1,3-bisdiphenylphosphine propane, ferrocene bisdiphenylphosphine, 4,5-bisdiphenylphosphine-9,9-dimethyloxy At least one of heteroanthracene and 4'-dimethylaminophenyl di-tert-butyl phosphine is preferably tri-tert-butyl phosphine; the base may be selected from lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, At least one of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, potassium phosphate, triethylamine, and diisopropylethylamine is preferably sodium tert-butoxide. As a result, the reaction rate can be further increased, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -N bond coupling reaction is carried out in a first solvent, and the first solvent may include selected from the group consisting of chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2,2-Tetrachloroethane, benzene, toluene, benzotrifluoride, fluorobenzene, nitrobenzene, o-xylene, m-xylene, p-xylene, mixed xylene, trimethylbenzene and tetralin At least one of them is preferably toluene. As a result, the difficulty of post-processing can be further reduced, and the production cost can be reduced.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -N bond coupling reaction is completed at 25-200° C. for 0.1-96 h, preferably at 110° C. for 24 h. Thus, while providing mild and easy-to-control temperature conditions for the reaction, the conversion rate of the raw materials and the yield of the reaction can be ensured.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -N bond coupling reaction, the amount ratio of the compound represented by formula (VIII) to the first transition metal catalyst is 0.01 to 1 mmol: 0.01 to 100 mmol, preferably 1.0 mmol: 0.5mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -N bond coupling reaction, the amount ratio of the compound represented by formula (VIII) to the phosphine ligand is 0.01-1mmol:0.01-100mmol, preferably 1.0mmol:1.0mmol . As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -N bond coupling reaction, the amount ratio of the compound represented by formula (VIII) to the base is 0.01-1 mmol: 0.001-10 mmol, preferably 1.0 mmol: 8.0 mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

In another aspect of the present disclosure, the present disclosure proposes a method for preparing the compound represented by formula (II) above. According to an embodiment of the present disclosure, the method includes: reacting the compound represented by formula (I-1) with R ^1b -X ⁰ to obtain the compound represented by formula (II); or, allowing the compound represented by formula (IX) to In the presence of the first transition metal catalyst, an intermolecular Csp ^{2 -N bond coupling reaction occurs with R 1b} -NH _{2 to} obtain a compound represented by formula (II);

Wherein, R ^b and R ^{1b are} as described above, and X ⁰ is Cl, Br or I.

According to the embodiments of the present disclosure, the compound represented by formula (I) reacts with a halide, or the compound represented by formula (IX) undergoes an intramolecular Csp ² -N bond coupling reaction under the catalysis of a transition metal to obtain the compound represented by formula (II) It shows the compound, the reaction conditions are mild, the obtained product is stable in the air and easy to separate and purify, and has good practicability and application prospects.

In addition, the method for preparing the compound represented by formula (II) according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

According to an embodiment of the present disclosure, the above-mentioned first transition metal catalyst may include selected from the group consisting of palladium chloride, palladium acetate, tris(dibenzylideneacetone)dipalladium, tris(dibenzylideneacetone)dipalladium chloroform complex, tetrabenzene At least one of phosphonium palladium and ferrocene bis(diphenylphosphine) palladium chloride. When the compound of formula (I) is used to prepare the compound of formula (II), the first transition metal catalyst is preferably tris(dibenzylidene acetone) dipalladium; when the compound of formula (IX) is used to prepare the compound of formula (II) In the case of the compound shown, the first transition metal catalyst is preferably a tris(dibenzylideneacetone)dipalladium chloroform complex. As a result, the reaction rate can be further increased, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -N bond coupling reaction is carried out under the action of a phosphine ligand and a base. The phosphine ligand may include selected from triphenylphosphine, tri-tert-butylphosphine, 1,1 '-Binaphthyl-2,2'-bisdiphenylphosphine, 1,3-bisdiphenylphosphine propane, ferrocene bisdiphenylphosphine, 4,5-bisdiphenylphosphine-9,9-dimethyloxy At least one of heteroanthracene and 4'-dimethylaminophenyl bis-tert-butyl phosphine. When the compound represented by formula (I-1) is used to prepare the compound represented by formula (II), the phosphine ligand is preferably 4'-dimethylaminophenyl bis-tert-butyl phosphine; when the compound represented by formula (IX) is used for preparation In the case of the compound represented by formula (II), the phosphine ligand is preferably 4,5-bisdiphenylphosphine-9,9-dimethylxanthene. The base may be selected from lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, potassium phosphate, triethylamine, diisopropylethylamine At least one of. When the compound represented by formula (I-1) is used to prepare the compound represented by formula (II), the base is preferably sodium tert-butoxide; when the compound represented by formula (IX) is used to prepare the compound represented by formula (II), the base is preferably It is potassium phosphate. As a result, the reaction rate can be further increased, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -N bond coupling reaction is carried out in a first solvent, and the first solvent may include selected from the group consisting of chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2,2-Tetrachloroethane, benzene, toluene, benzotrifluoride, fluorobenzene, nitrobenzene, o-xylene, m-xylene, p-xylene, mixed xylene, trimethylbenzene and tetralin At least one of them is preferably a commercial mixed xylene. As a result, the difficulty of post-processing can be further reduced, and the production cost can be reduced.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -N bond coupling reaction is completed at 25-200° C. for 0.1-96 h, preferably at 110° C. for 24 h. Thus, while providing mild and easy-to-control temperature conditions for the reaction, the conversion rate of the raw materials and the yield of the reaction can be ensured.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -N bond coupling reaction, the amount ratio of the compound represented by formula (I-1) or the compound represented by formula (IX) to the first transition metal catalyst is 0.01-1 mmol : 0.01-100mmol, preferably 1.0mmol:0.5mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -N bond coupling reaction, the amount ratio of the compound represented by formula (I-1) or the compound represented by formula (IX) and the phosphine ligand is 0.01-1mmol:0.01 ~100mmol, preferably 1.0mmol:1.0mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -N bond coupling reaction, the amount ratio of the compound represented by formula (I-1) or the compound represented by formula (IX) to the base is 0.01-1mmol:0.001-10mmol , Preferably 1.0mmol:8.0mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

In another aspect of the present disclosure, the present disclosure proposes a method for preparing the compound represented by formula (III) and the compound represented by formula (VI). According to an embodiment of the present disclosure, the method includes:

(1) Preparation of compound represented by formula (X) and compound represented by formula (XII)

Make the compound of formula (IX) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a second transition metal catalyst, or make the compound of formula (IX) undergo a hydrolysis reaction and intramolecular aromatic nucleophilic substitution Reaction to obtain the compound represented by formula (X);

Make the compound of formula (XI) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a second transition metal catalyst, or make the compound of formula (XI) undergo a hydrolysis reaction and intramolecular aromatic nucleophilic substitution Reaction to obtain the compound represented by formula (XII);

(2) Preparation of compound represented by formula (III) and compound represented by formula (VI)

Make the compound of formula (X) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a transition metal catalyst, or make the compound of formula (X) undergo a hydrolysis reaction and an intramolecular aromatic nucleophilic substitution reaction, The compound represented by formula (III) is obtained;

Make the compound of formula (XII) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a second transition metal catalyst, or make the compound of formula (XII) undergo a hydrolysis reaction and intramolecular aromatic nucleophilic substitution React to obtain the compound represented by formula (VI);

Wherein, R ^c is as described above.

According to the embodiments of the present disclosure, the compound represented by formula (IX) undergoes an intramolecular Csp ² -O bond coupling reaction, or undergoes a hydrolysis reaction and an intramolecular aromatic nucleophilic substitution reaction in the presence of a second transition metal catalyst. The prepared compound represented by formula (X); the compound represented by formula (IX) undergoes intramolecular Csp ² -O bond coupling reaction in the presence of a second transition metal catalyst, or undergoes hydrolysis reaction and intramolecular aromatic nucleophilic By substitution reaction, the compound represented by formula (XII) can be prepared. Furthermore, the compound represented by formula (X) undergoes an intramolecular Csp ² -O bond coupling reaction, or undergoes a hydrolysis reaction and an intramolecular aromatic nucleophilic substitution reaction in the presence of a second transition metal catalyst, and the formula ( III) The compound shown in the formula (XII), in the presence of the second transition metal catalyst, undergoes an intramolecular Csp ² -O bond coupling reaction, or undergoes a hydrolysis reaction and an intramolecular aromatic nucleophilic substitution reaction, and can be prepared The obtained compound represented by formula (VI). The above reaction conditions are mild, the obtained product is stable in the air and easy to separate and purify, and has good practicability and application prospects.

In addition, the method for preparing the compound represented by formula (III) and the compound represented by formula (VI) according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

According to an embodiment of the present disclosure, the above-mentioned second transition metal catalyst may include palladium acetate, palladium chloride, tetrakis(triphenylphosphine)palladium, [1,1'-bis(diphenylphosphine)ferrocene]dichloride Palladium, [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium dichloromethane complex, bistriphenylphosphine palladium dichloride, tris(dibenzylideneacetone)dipalladium (0), three (dibenzylidene acetone) two palladium (0) chloroform complex, bis (dibenzylidene acetone) palladium (0), allyl palladium chloride (II) dimer, two (benzene Nitrile) palladium dichloride, bis(acetonitrile) palladium dichloride, 1,4-bis(diphenylphosphine)butane-palladium(II) chloride, bis(methyldiphenylphosphine)palladium dichloride ( II), 1,1'-bis(di-tert-butylphosphine)ferrocene palladium dichloride, bis(tri-o-toluenephosphine)palladium(II), bis(tricyclohexylphosphine)palladium dichloride At least one of [1,3-bis(diphenylphosphine)propane]palladium(II) chloride and bis(tri-tert-butylphosphine)palladium, preferably tetrakis(triphenylphosphine)palladium. As a result, the reaction rate can be further increased, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -O bond coupling reaction is carried out under the action of a phosphine ligand and a base. The phosphine ligand may be selected from the group consisting of triphenylphosphine and 2-bicyclohexylphosphine-2', 4',6'-Triisopropylbiphenyl, 2-Biscyclohexylphosphine-2',6'-Dimethoxybiphenyl, 2-Biscyclohexylphosphine-2',6'-Diisopropoxy-1 ,1'-biphenyl, 4,5-bisdiphenylphosphine-9,9-dimethylxanthene, 1,1'-bis(diphenylphosphine)ferrocene, 1,1'-biphenyl At least one of dinaphthol, 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl, tricyclohexylphosphine, and tri-tert-butylphosphine, preferably triphenylphosphine; The base includes selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, potassium phosphate, sodium phosphate, sodium tert-butoxide, potassium tert-butoxide, dipotassium hydrogen phosphate, triethylamine, N,N-dimethylaminopyridine At least one of DBU is preferably potassium phosphate. As a result, the reaction rate can be further increased, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -O bond coupling reaction, hydrolysis reaction, and intramolecular aromatic nucleophilic substitution reaction are carried out in a third solvent, and the third solvent may include selected from acetonitrile, tetrahydrofuran, xylene, 1,4-Dioxane, tetralin, dimethyl sulfoxide, chlorobenzene, o-dichlorobenzene, benzylacetonitrile, nitrobenzene, N,N-dimethylformamide, dimethyl sulfoxide, At least one of N,N-dimethylacetamide, hexamethylphosphoric triamide, and N-methylpyrrolidone is preferably N,N-dimethylformamide. As a result, the reaction rate can be further increased, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned intramolecular Csp ² -O bond coupling reaction is completed at 0-150° C. for 0.1-96 h. For the compound represented by formula (IX) to prepare the compound represented by formula (X), the intramolecular Csp ² -O bond coupling reaction is preferably completed at 100° C. for 18 hours; for the compound represented by formula (XI), formula (XII) is prepared The intramolecular Csp ² -O bond coupling reaction of the compound is preferably completed at 100° C. for 24 hours. Therefore, it is possible to provide mild temperature conditions for the reaction, reduce the degree of continuous conversion of products due to staying in the system, and ensure the conversion rate of the raw materials and the yield of the reaction.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -O bond coupling reaction, the amount ratio of the compound represented by formula (IX) or the compound represented by formula (XI) to the second transition metal catalyst may be 0.1 to 1 mmol: 0.01-0.1 mmol, the dosage ratio of the compound represented by formula (IX) to the second transition metal catalyst is preferably 1 mmol: 0.25 mmol, and the dosage ratio of the compound represented by formula (XI) to the second transition metal catalyst is preferably 0.3 mmol: 0.15 mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -O bond coupling reaction, the amount ratio of the compound represented by formula (IX) or the compound represented by formula (XI) and the phosphine ligand may be 0.01-1 mmol:0.01- 100mmol, the usage ratio of the compound represented by formula (IX) to the phosphine ligand is preferably 1mmol:0.5mmol, and the usage ratio of the compound represented by formula (XI) to the phosphine ligand is preferably 0.3mmol:0.6mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

According to an embodiment of the present disclosure, in the above-mentioned intramolecular Csp ² -O bond coupling reaction, the amount ratio of the compound represented by formula (X) or the compound represented by formula (XI) to the base can be 0.01-1mmol:0.001-10mmol The amount ratio of the compound shown in (IX) to the base is preferably 1 mmol: 6 mmol, and the amount ratio of the compound shown in formula (XI) to the base is preferably 0.3 mmol: 1.8 mmol. As a result, a faster conversion rate of raw materials can be ensured, and synthesis costs can be reduced at the same time.

According to the embodiments of the present disclosure, the above-mentioned hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction are completed at 0-150° C. for 0.1-96 h. For the compound represented by formula (IX) to prepare the compound represented by formula (X), the hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction are preferably completed at 60°C for 6 hours; for the compound represented by formula (XI), formula (XII) is prepared The hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction of the compound shown are preferably completed at 60°C for 6 hours. For the compound represented by formula (X) to prepare the compound represented by formula (III), the hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction are preferably completed at 100°C for 24 hours; for the compound represented by formula (XII), formula (VI) is prepared The hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction of the compound shown are preferably completed at 120°C for 10 hours. Therefore, it is possible to provide mild temperature conditions for the reaction, reduce the degree of continuous conversion of products due to staying in the system, and ensure the conversion rate of the raw materials and the yield of the reaction.

According to the embodiments of the present disclosure, in the above-mentioned hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (X) to the base used in the hydrolysis reaction is 0.01-1mmol:0.001-10mmol, preferably 1.5mmol : 8mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, in the hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (IX) and the base used in the hydrolysis reaction is 0.01-1mmol:0.001-10mmol, preferably 1.5mmol : 8mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, in the above-mentioned hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (XI) to the base used in the hydrolysis reaction is 0.01-1mmol:0.001-10mmol, preferably 0.3mmol : 1.8mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, in the above hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (XII) to the base used in the hydrolysis reaction is 0.01-1mmol:0.001-10mmol, preferably 0.06mmol : 0.4mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

In another aspect of the present disclosure, the present disclosure proposes a method for preparing the compound represented by formula (III) and the compound represented by formula (VI). According to an embodiment of the present disclosure, the method includes:

The compound represented by formula (IX) or the compound represented by formula (XIII) is subjected to selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction in sequence under the action of a base to obtain the compound represented by formula (III);

The compound represented by formula (XI) or the compound represented by formula (XIV) is subjected to selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction in sequence under the action of a base to obtain the compound represented by formula (VI);

Wherein, R ^c is as described above.

According to the method for preparing the compound represented by formula (III) and the compound represented by formula (VI) according to the embodiments of the present disclosure, the trifluoromethanesulfonyl group is selectively hydrolyzed to a hydroxyl group, or the corresponding position of the trifluoromethanesulfonyl group is directly used for the hydroxyl group. The raw material, and then through the intramolecular aromatic nucleophilic substitution reaction, the compound represented by the formula (III) and the compound represented by the formula (VI) are prepared. The above reaction conditions are mild, the obtained product is stable in the air and easy to separate and purify, and has good practicability and application prospects.

In addition, the method for preparing the compound represented by formula (III) and the compound represented by formula (VI) according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

According to an embodiment of the present disclosure, in the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the base used may be selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, potassium phosphate, sodium phosphate, tert-butyl At least one of sodium alkoxide, potassium tert-butoxide, dipotassium hydrogen phosphate, triethylamine, N,N-dimethylaminopyridine, and DBU. For the reaction of the compound of formula (IX) to prepare the compound of formula (III) and the reaction of the compound of formula (XI) to prepare the compound of formula (VI), the base is preferably potassium phosphate; for the reaction of formula (XIII) In the reaction of the compound to prepare the compound of formula (III) and the reaction of the compound of formula (XIV) to prepare the compound of formula (VI), the base is preferably potassium carbonate. As a result, the reaction rate can be further increased, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction are carried out in a fourth solvent, and the fourth solvent may include selected from acetonitrile, tetrahydrofuran, 1,4-dioxane, N, N -At least one of dimethylformamide, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone, benzylacetonitrile, and nitrobenzene, preferably It is N,N-dimethylformamide. As a result, the reaction rate can be further increased, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction can be completed at 0-150°C for 0.1-96 hours. For the reaction of the compound of formula (IX) to prepare the compound of formula (III), it is preferably completed at 120°C for 24 hours; for the reaction of the compound of formula (XIII) to prepare the compound of formula (III), the reaction of formula (XIV) The reaction of preparing the compound of formula (VI) from the compound shown in) and the reaction of preparing the compound of formula (VI) from the compound of formula (XI) are preferably completed at 100° C. for 24 hours. As a result, the reaction rate can be further increased, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, in the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (IX) to the base is 0.01-1mmol: 0.001-10mmol, preferably 0.36mmol: 2.16mmol . As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, in the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (XI) to the base is 0.01-1mmol: 0.001-10mmol, preferably 0.36mmol: 2.16mmol . As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, in the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (XIII) to the base is 0.01-1mmol:0.001-20mmol, preferably 1mmol:11.0mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to the embodiments of the present disclosure, in the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (XIV) to the base is 0.01-1 mmol: 0.001-20 mmol, preferably 1 mmol: 12.0 mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

In another aspect of the present disclosure, the present disclosure provides a method for preparing the compound represented by formula (V), the compound represented by (IV), and the compound represented by formula (VII). According to an embodiment of the present disclosure, the method includes:

(1) Preparation of compound represented by formula (XV)

The compound represented by formula (X-1) is subjected to the first intermolecular Csp ² -heterobond coupling reaction and the first intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by formula (XV); An intermolecular Csp ² -heterobond coupling reaction and the first intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst and R ^1d -NH ₂ ;

(2) Preparation of compound represented by formula (IV)

The compound represented by formula (X-1) is subjected to the second intermolecular Csp ² -heterobond coupling reaction and the second intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by formula (IV). ^{The Csp 2} -heterobond coupling reaction between two molecules and the second intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst, R ^1d -NH ₂ , and R ^2d -NH ₂ ;

Alternatively, the compound represented by formula (XV) is subjected to a third intermolecular Csp ² -heterobond coupling reaction and a third intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by formula (IV); The three intermolecular Csp ² -heterobond coupling reaction and the third intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst and R ^2d -NH ₂ ;

(3) Preparation of compound represented by formula (VII)

The compound represented by the formula (XII-1) is subjected to the fourth intermolecular Csp ² -heterobond coupling reaction and the fourth intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by the formula (VII); The four-molecular Csp ² -heterobond coupling reaction and the fourth intramolecular Csp ² -heterobond coupling reaction are performed on the second transition metal catalyst and R ^1d -NH ₂ , R ^2d -NH ₂ , R ^3d -NH ₂ Under existing conditions;

(4) Preparation of compound represented by formula (V)

The compound represented by formula (X-1) is subjected to the fifth intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by formula (V). The five intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst and R ^1d -NH ₂ ;

Alternatively, the compound represented by the formula (XV) is subjected to the sixth intermolecular Csp ² -heterobond coupling reaction and the sixth intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by the formula (V); The six intermolecular Csp ² -heterobond coupling reaction and the sixth intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst;

Alternatively, the compound represented by formula (XV) is subjected to selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction in sequence under the action of a base to obtain the compound represented by formula (V);

In addition, the method for preparing the compound represented by formula (V), the compound represented by (IV), and the compound represented by formula (VII) according to the foregoing embodiments of the present disclosure may also have the following additional technical features:

According to an embodiment of the present disclosure, the above-mentioned second transition metal catalyst may include selected from palladium acetate, palladium chloride, tetrakis(triphenylphosphine)palladium, [1,1'-bis(diphenylphosphine)ferrocene] Palladium dichloride, [1,1'-bis(diphenylphosphine)ferrocene] palladium dichloride dichloromethane complex, bistriphenylphosphine palladium dichloride, tris(dibenzylidene acetone) Two palladium (0), three (dibenzylidene acetone) two palladium (0) chloroform complex, bis (dibenzylidene acetone) palladium (0), allyl palladium chloride (II) dimer, two (Benzonitrile) palladium dichloride, bis(acetonitrile) palladium dichloride, 1,4-bis(diphenylphosphine)butane-palladium(II) chloride, bis(methyldiphenylphosphine) dichloride Palladium(II), 1,1'-bis(di-tert-butylphosphine)ferrocene palladium dichloride, bis(tri-o-toluenephosphine)palladium(II), bis(tricyclohexylphosphine)dichloride At least one of palladium chloride, [1,3-bis(diphenylphosphine)propane]palladium(II) chloride, and bis(tri-tert-butylphosphine)palladium. For the first to fourth intermolecular Csp ² -heterobond coupling reactions and the first to fourth intramolecular Csp ² -heterobond coupling reactions, the second transition metal catalyst is preferably tris(dibenzylideneacetone)dipalladium (0) Chloroform complex, for the fifth intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction, the second transition metal catalyst is preferably three (dibenzylidene acetone) two Palladium (0), for the sixth intermolecular Csp ² -heterobond coupling reaction and the sixth intramolecular Csp ² -heterobond coupling reaction, the second transition metal catalyst is preferably tetrakistriphenylphosphine palladium. As a result, the reaction rate can be increased, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the first intermolecular Csp ² -heterobond coupling reaction, the first intramolecular Csp ^{2 -heterobond coupling reaction, the second intermolecular Csp 2} -heterobond coupling reaction, the second intramolecular Csp 2 -heterobond coupling reaction, Csp ² -heterobond coupling reaction, third intermolecular Csp ² -heterobond coupling reaction, third intramolecular Csp ² -heterobond coupling reaction, fourth intermolecular Csp ² -heterobond coupling reaction, fourth Intramolecular Csp ² -heterobond coupling reaction, fifth intermolecular Csp ² -heterobond coupling reaction, fifth intramolecular Csp ² -heterobond coupling reaction, sixth intermolecular Csp ² -heterobond coupling reaction, The sixth intramolecular Csp ² -heterobond coupling reaction is carried out under the action of a phosphine ligand and a base. The phosphine ligand may include a group selected from triphenylphosphine, 2-bicyclohexylphosphine-2',4',6'- Triisopropylbiphenyl, 2-Biscyclohexylphosphine-2',6'-Dimethoxybiphenyl, 2-Biscyclohexylphosphine-2',6'-Diisopropoxy-1,1'-Biphenyl , 4,5-bisdiphenylphosphine-9,9-dimethylxanthene, 1,1'-bis(diphenylphosphine)ferrocene, 1,1'-binaphthol, 2, At least one of 2'-bis-(diphenylphosphino)-1,1'-binaphthalene, tricyclohexylphosphine, and tri-tert-butylphosphine. For the first to fourth intermolecular Csp ² -heterobond coupling reaction and the first to fourth intramolecular Csp ² -heterobond coupling reaction, the phosphine ligand is preferably 4,5-bisdiphenylphosphine-9, 9-Dimethylxanthene, for the fifth intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction, the phosphine ligand is preferably 4,5-bisdiphenylphosphine -9,9-Dimethylxanthene, for the sixth intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction, the phosphine ligand is preferably triphenylphosphine. As a result, the reaction rate can be increased, and the selectivity and yield of the reaction can be improved. The base may include selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, sodium acetate, potassium acetate, lithium acetate, potassium phosphate, sodium phosphate, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, tert-butanol At least one of potassium, tetrabutylammonium hydroxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, triethylamine, diethylamine, N,N-diisopropylethylamine, and DBU is preferably potassium phosphate. As a result, the reaction rate and the conversion rate of raw materials can be further increased, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the first intermolecular Csp ² -heterobond coupling reaction, the first intramolecular Csp ² -heterobond coupling reaction, the second intermolecular Csp ² -heterobond coupling reaction, the second molecule Internal Csp ² -heterobond coupling reaction, third intermolecular Csp ² -heterobond coupling reaction, third intramolecular Csp ² -heterobond coupling reaction, fourth intermolecular Csp ² -heterobond coupling reaction, first Four-molecular Csp ² -hetero-bond coupling reaction, fifth intermolecular Csp ² -hetero-bond coupling reaction, fifth intra-molecular Csp ² -hetero-bond coupling reaction, sixth intermolecular Csp ² -hetero-bond coupling reaction , The sixth intramolecular Csp ² -heterobond coupling reaction is carried out in the fifth solvent, the fifth solvent includes selected from xylene, 1,1,2,2-tetrachloroethane, benzene, toluene, trifluorotoluene, At least one of chlorobenzene, fluorobenzene, nitrobenzene, bromobenzene, o-xylene, meta-xylene, p-xylene, N,N-dimethylformamide, and tetralin. For the first to fifth intermolecular Csp ² -heterobond coupling reactions and the first to fifth intramolecular Csp ² -heterobond coupling reactions, the fifth solvent is preferably xylene. For the sixth intermolecular Csp ^{2 -heterobond} For the bond coupling reaction and the sixth intramolecular Csp ² -heterobond coupling reaction, the fifth solvent is preferably N,N-dimethylformamide. As a result, the reaction rate can be increased, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the first intermolecular Csp ² -heterobond coupling reaction, the first intramolecular Csp ^{2 -heterobond coupling reaction, the second intermolecular Csp 2} -heterobond coupling reaction, the second intramolecular Csp 2 -heterobond coupling reaction, Csp ² -heterobond coupling reaction, third intermolecular Csp ² -heterobond coupling reaction, third intramolecular Csp ² -heterobond coupling reaction, fourth intermolecular Csp ² -heterobond coupling reaction, fourth Intramolecular Csp ² -heterobond coupling reaction, fifth intermolecular Csp ² -heterobond coupling reaction, fifth intramolecular Csp ² -heterobond coupling reaction can, sixth intermolecular Csp ² -heterobond coupling reaction , The sixth intramolecular Csp ² -heterobond coupling reaction is completed at 0～200℃ for 0.1～96h. The first intermolecular Csp ² -heterobond coupling reaction, the first intramolecular Csp ² -heterobond coupling reaction is preferably completed at 150°C for 6 hours, the second intermolecular Csp ² -heterobond coupling reaction, the second molecule The internal Csp ² -heterobond coupling reaction is preferably carried out at 150°C for 48h, and the third intermolecular Csp ² -heterobond coupling reaction and the third intramolecular Csp ² -heterobond coupling reaction are preferably carried out at 150°C for 30h. Complete, the fourth intermolecular Csp ² -heterobond coupling reaction, the fourth intramolecular Csp ² -heterobond coupling reaction is preferably completed at 150 ℃ for 48h, the fifth intermolecular Csp ² -heterobond coupling reaction, the fifth intermolecular Csp 2 -heterobond coupling reaction, The five intramolecular Csp ² -heterobond coupling reaction is preferably completed at 150°C for 30h, the sixth intermolecular Csp ² -heterobond coupling reaction, the sixth intramolecular Csp ² -heterobond coupling reaction is preferably at 140°C Proceed for 20h to complete. Therefore, mild temperature conditions can be provided for the reaction, and the conversion rate of the raw materials and the yield of the reaction can be ensured.

According to the embodiment of the present disclosure, in the first intermolecular Csp ² -heterobond coupling reaction and the first intramolecular Csp ² -heterobond coupling reaction, the compound represented by formula (X-1) and R ^1d -NH ₂ The dosage ratio is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 2 mmol; the dosage ratio of the compound represented by formula (X-1) to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.1 mmol; the dosage ratio of the compound represented by formula (X-1) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.4 mol; the dosage ratio of the compound represented by formula (X-1) to the base is 0.0001 ~1mol:0.0001-20mol, preferably 1mmol:6mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, in the second intermolecular Csp ² -heterobond coupling reaction and the second intramolecular Csp ² -heterobond coupling reaction, the compound represented by formula (X-1) and R ^1d- The dosage _{ratio of NH 2} is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 4 mmol; the dosage ^{ratio of the compound represented by formula (X-1) to R 2d} -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol : 4mmol; the amount ratio of the compound represented by the formula (X-1) to the second transition metal catalyst is 0.0001～1mol:0.0001～10mol, preferably 1mmol:0.2mmol; the compound represented by the formula (X-1) and the phosphine ligand The dosage ratio is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.8 mmol; the dosage ratio of the compound represented by formula (X-1) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol, preferably 1 mmol: 12 mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, in the foregoing third intermolecular Csp ² -heterobond coupling reaction and the third intramolecular Csp ² -heterobond coupling reaction, the compound represented by formula (XV) and R ^2d -NH ₂ The dosage ratio is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 2 mmol; the dosage ratio of the compound represented by formula (XV) to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.1 mmol; The dosage ratio of the compound represented by formula (XV) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.4 mmol; the dosage ratio of the compound represented by formula (XV) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol , Preferably 1mmol:6mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, in the fourth intermolecular Csp ² -heterobond coupling reaction and the fourth intramolecular Csp ² -heterobond coupling reaction, the compound represented by formula (XII-1) and R ^1d- The dosage _{ratio of NH 2} is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 6 mmol, and the ^dosage ratio of the compound represented by formula (XII-1) to R 2d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol : 6mmol, the amount ratio of the compound represented by formula (XII-1) to R ^3d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 6 mmol; the compound represented by formula (XII-1) and the second transition metal The dosage ratio of the catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.3 mmol; the dosage ratio of the compound represented by formula (XII-1) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 1.2 mmol; The amount ratio of the compound represented by the formula (XII-1) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol, preferably 1 mmol: 18 mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, in the fifth intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction, the compound represented by formula (X-1) and the The dosage ratio of the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.2 mmol; the dosage ratio of the compound represented by formula (X-1) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol , Preferably 1 mmol: 0.8 mol; the amount ratio of the compound represented by formula (X-1) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol, preferably 1 mmol: 12 mmol; the compound represented by formula (X-1) and R ^The amount ratio of 1d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 1 mmol. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, in the sixth intermolecular Csp ² -heterobond coupling reaction and the sixth intramolecular Csp ² -heterobond coupling reaction, the compound represented by formula (XV) and the second transition metal catalyst The dosage ratio is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.25 mmol; the dosage ratio of the compound represented by formula (XV) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 0.5 mol; The amount ratio of the compound shown in (XV) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol, preferably 1 mmol: 6 mmol. As a result, a faster conversion rate of raw materials can be ensured, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, in the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the base used is selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, potassium phosphate, sodium phosphate, tert-butanol At least one of sodium, potassium tert-butoxide, dipotassium hydrogen phosphate, triethylamine, N,N-dimethylaminopyridine, and DBU is preferably potassium phosphate. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction are carried out in a sixth solvent, and the sixth solvent includes selected from acetonitrile, tetrahydrofuran, 1,4-dioxane, N, At least one of N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone, benzylacetonitrile, and nitrobenzene, Preferably, it is N,N-dimethylformamide. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction are completed at 0-200°C for 0.1-96 hours, preferably at 140°C for 20 hours. As a result, a faster conversion rate of raw materials can be ensured, the degree of continuous conversion of products due to staying in the system can be reduced, and the selectivity and yield of the reaction can be improved.

According to an embodiment of the present disclosure, in the above-mentioned selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (XV) to the base is 0.0001 to 1 mol: 0.0001 to 10 mol, preferably 1 mmol: 6 mmol; Therefore, it is possible to ensure a faster conversion rate of raw materials, reduce the degree of continuous conversion of products due to staying in the system, and improve the selectivity and yield of the reaction.

The additional aspects and advantages of the present disclosure will be partially given in the following description, and some will become obvious from the following description, or be understood through the practice of the present disclosure.

Description of the drawings

The above and/or additional aspects and advantages of the present disclosure will become obvious and easy to understand from the description of the embodiments in conjunction with the following drawings, in which:

Figure 1 is the hydrogen nuclear magnetic spectrum of the compound represented by formula (Ia);

Figure 2 is the NMR spectrum of the compound represented by formula (Ia);

Figure 3 is an X-ray single crystal diffraction pattern of the compound represented by formula (Ia);

Figure 4 is the hydrogen nuclear magnetic spectrum of the compound represented by formula (IIa);

Figure 5 is a nuclear magnetic carbon spectrum of the compound represented by formula (IIa);

Figure 6 is an X-ray single crystal diffraction pattern of the compound represented by formula (IIa);

Figure 7 is a hydrogen nuclear magnetic spectrum of the compound represented by formula (IIIa);

Figure 8 is a nuclear magnetic carbon spectrum of the compound represented by formula (IIIa);

Figure 9 is an X-ray single crystal diffraction pattern of the compound represented by formula (IIIa);

Figure 10 is a hydrogen nuclear magnetic spectrum of the compound represented by formula (IVa);

Figure 11 is a nuclear magnetic carbon spectrum of the compound represented by formula (IVa);

Figure 12 is an X-ray single crystal diffraction pattern of the compound represented by formula (IVa);

Figure 13 is a hydrogen nuclear magnetic spectrum of the compound represented by formula (Va);

Figure 14 is a nuclear magnetic carbon spectrum of the compound represented by formula (Va);

Figure 15 is an X-ray single crystal diffraction pattern of the compound represented by formula (Va);

Figure 16 is a hydrogen nuclear magnetic spectrum of the compound represented by formula (VIa);

Figure 17 is a nuclear magnetic carbon spectrum of the compound represented by formula (VIa);

Figure 18 is an X-ray single crystal diffraction pattern of the compound represented by formula (VIa).

Detailed ways

The embodiments of the present disclosure are described in detail below. The embodiments described below are exemplary, and are only used to explain the present disclosure, and should not be construed as limiting the present disclosure. Where specific techniques or conditions are not indicated in the examples, the procedures shall be carried out in accordance with the techniques or conditions described in the literature in the field or in accordance with the product specification. The reagents or instruments used without the manufacturer's indication are all conventional products that can be purchased commercially.

Example 1: Preparation of compound (Ia) (corresponding to R ^{a in} formula (I) is Et)

The reaction formula is as follows:

The specific preparation method is:

Add 0.75mmol (636mg) of the compound represented by formula (VIIIa), 0.075mmol (68mg) tris(dibenzylideneacetone) dipalladium and 5mmol (500mg) sodium tert-butoxide into a 100mL round bottom flask, and add 50mL deoxygenated toluene , Add 0.3mL 1mol/L tri-tert-butylphosphine toluene solution and reflux for 24h. Cool to room temperature, add 230-400 mesh silica gel, spin dry to prepare samples. The stationary phase is 230-400 mesh silica gel, and the mobile phase ranges from petroleum ether: ethyl acetate = 3:1 to petroleum ether: ethyl acetate = 1:2. Column chromatography is performed to separate and purify, and 249 mg of the compound shown in (Ia) can be obtained. An orange powdery solid with a yield of 63%. The X-ray single crystal diffraction pattern of the product is shown in Figure 3.

¹ H NMR(400MHz,CDCl ₃ )δ6.53(s,4H),6.42(s,4H),5.23(b,4H)3.22(t,J=7.6Hz,4H),2.09(quin,J=7.2 Hz, 8H), 1.27 (t, J = 7.2 Hz, 12H); (Figure 1)

¹³ C NMR(100MHz,CDCl ₃ )δ150.4,129.9,117.7,111.2,42.2,18.9,12.8; (Figure 2)

_{HRMS (-p ESI) Calc.for C 36} H 35 N 4 [MH] - 523.2867, Found 523.2863.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Ia).

Example 2: Preparation of compound (IIa) (corresponding to formula (II) where R ^b is Et and R ^1b is Ph)

The reaction formula is as follows:

The specific preparation method is:

Add 0.125mmol (65mg) of the compound represented by formula (Ia), 0.01mmol (10mg) tris(dibenzylideneacetone) dipalladium and 0.2mmol (10mg) 4'-dimethylaminophenyl di-tert Add butyl phosphine, add 50 mL deoxygenated xylene, add 0.3 mL bromobenzene, and reflux for 48 hours. The xylene was evaporated, 50 mL of dichloromethane was added to dissolve, washed with 50 mL of water and 50 mL of saturated sodium chloride solution, and dried with anhydrous sodium sulfate. Remove the sodium sulfate, add 230-400 mesh silica gel, and spin dry for sample preparation. The stationary phase is 230-400 mesh silica gel, and the mobile phase ranges from petroleum ether: dichloromethane = 10:1 to petroleum ether: dichloromethane = 3:1. After column chromatography is performed, 98 mg of the compound shown in (IIa) can be obtained. The white powdery solid, the yield is 94%, and the X-ray single crystal diffraction pattern of the product is shown in Figure 6.

¹ H NMR (400MHz, CDCl ₃ , TMS) δ 7.68 (s, 4H), 7.30-7.27 (m, 16H), 6.83-6.79 (m, 4H), 6.68 (s, 4H), 3.46 (t, J =7.2Hz, 4H), 2.12 (quin, J = 7.6Hz, 8H), 1.26 (t, J = 7.2Hz, 12H); (Figure 4)

¹³ C NMR (100MHz, CDCl ₃ , TMS) δ145.6,142.9,141.2,129.3,125.0,118.6,118.5,112.6,43.2,18.6,12.5; (Figure 5)

HRMS(MARDI)Calc.for C ₆₀ H ₅₂ N ₄ [M] ⁺ 828.4186,Found 828.4186.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (IIa).

Example 3: Preparation of compound (IIe) (corresponding to formula (II) where R ^b is Et and R ^1b is 4-Me-C ₆ H ₄ )

The reaction formula is as follows:

The specific preparation method is:

Add 0.25mmol (414mg) of the compound represented by formula (IXa), 0.1mmol (100mg) tris(dibenzylideneacetone) dipalladium chloroform complex, 0.2mmol (100mg) 4,5-bisdiphenyl into a 100mL round bottom flask Phosphine-9,9-dimethylxanthene, 2.0mmol (250mg) p-anisidine and 1g potassium phosphate, add 50mL deoxygenated xylene and reflux for 72h. The xylene was evaporated, 50 mL of dichloromethane was added to dissolve, washed with 50 mL of water and 50 mL of saturated sodium chloride solution, and dried with anhydrous sodium sulfate. Remove the sodium sulfate, add 230-400 mesh silica gel, and spin dry for sample preparation. The stationary phase is 230-400 mesh silica gel, and the mobile phase ranges from petroleum ether: dichloromethane=30:10 to petroleum ether: dichloromethane: ethyl acetate=30:10:1. After column chromatography separation and purification, (IIe ) The compound shown is 20 mg, a white powdery solid, and the yield is 5%.

¹ H NMR (400MHz, CDCl ₃ , TMS) δ7.66 (s, 4H), 7.24 (d, J = 9.2Hz, 8H), 6.85 (d, J = 9.2Hz, 8H), 6.64 (s, 4H) ,3.79(s,12H),3.42(t,J=7.2Hz,4H), 2.11(quin,J=7.4Hz,8H), 1.26(t,J=7.2Hz,12H);

¹³ C NMR (100MHz, CDCl ₃ , TMS) δ 152.5, 146.1, 140.4, 137.2, 124.0, 118.4, 114.7, 113.9, 55.8, 43.2, 18.6, 12.5;

HRMS(MARDI)Calc.for C ₆₄ H ₆₀ N ₄ O ₄ [M] ⁺ 948.4609,Found 948.4608.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (IIe).

Example 4: Preparation of compound (VIIIa) (corresponding to R ^{a in} formula (VIII) is Et)

The reaction formula is as follows:

The specific preparation method is:

Add 25mmol (27g) CAS No. 2226413-77-8 compound, 4mmol (1g) palladium acetate, 10mmol (6.7g) 1,1'-binaphthalene 2,2'-bisdiphenylphosphine into a 2000mL round bottom flask , And 150mmol (50g) cesium carbonate, add 1000mL deoxygenated dry toluene, add 120mmol (34mL) benzophenone imine, reflux for 48h. Distill toluene off, add 500mL of dichloromethane to dissolve, filter out the insolubles, slowly add 30mL 30% hydrogen peroxide and stir until no bubbles are generated, wash with 500mL of water, and dry with anhydrous sodium sulfate. Remove the sodium sulfate, add 230-400 mesh silica gel, and spin dry for sample preparation. The stationary phase is 230-400 mesh silica gel, and the mobile phase ranges from petroleum ether: dichloromethane=30:10 to petroleum ether: dichloromethane: ethyl acetate=30:10:1. After column chromatography separation and purification, (int I) The compound shown is 28.5 g, a yellow solid, and the yield is 94%.

¹ H NMR (400MHz, CDCl ₃ , TMS) δ7.49-7.29 (m, 24H), 6.88 (t, J = 7.6 Hz, 4H), 6.61 (t, J = 7.6 Hz, 8H), 6.53-6.47 ( m, 12H), 5.94 (d, J = 8.0 Hz, 4H), 4.16-4.12 (m, 4H), 2.26-2.06 (m, 8H), 0.89 (t, J = 7.6 Hz, 12H);

¹³ C NMR (100MHz, CDCl ₃ , TMS) δ 166.1, 146.3, 140.7, 139.4, 138.5, 135.3, 129.9, 129.3, 129.2, 128.7, 128.5, 127.8, 127.6, 124.5, 118.1, 47.5, 29.3, 12.8;

HRMS(+p ESI)Calc.for C ₈₈ H ₇₇ N ₄ [M+H] ⁺ 1189.6143,Found 1189.6176.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (int I).

Add 4mmol (5g) of the compound represented by formula (int I), 100mL methanol, 15mL water, 3mL 38% hydrochloric acid to a 250mL round bottom flask, stir at room temperature for 4h, add 5g sodium carbonate powder, and stir at room temperature for 4h. The methanol was evaporated, 250 mL of water, 250 mL of saturated sodium chloride solution, and 1000 mL of ethyl acetate were added for three extractions, and the combined organic phases were dried with anhydrous sodium sulfate. After removing sodium sulfate, evaporating most of the ethyl acetate, adding petroleum ether to make the product completely precipitate out, and filtering with suction to obtain 1.94 g of the compound shown in (int II), a white or slightly colored solid, with a yield of 92%.

¹ H NMR (400MHz, DMSO-d ₆ , TMS) δ 6.94 (s, 4H), 6.77 (d, J = 7.6 Hz, 4H), 6.42 (d, J = 7.6 Hz, 4H), 4.48 (s, 8H), 3.59 (t, J = 7.6 Hz, 4H), 1.93-1.84 (m, 8H), 0.79 (t, J = 6.8 Hz, 12H);

¹³ C NMR (400MHz, DMSO-d ₆ ) δ143.3, 131.7, 129.9, 127.4, 124.0, 114.7, 45.2, 28.3, 12.6;

HRMS(+p ESI)Calc.for C ₃₆ H ₄₅ N ₄ [M+H] ⁺ 533.3639,C ₃₆ H ₄₄ N ₄ Na[M+Na] ⁺ 555.3458,Found 533.3625,555.3443.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (int II).

Add 4mmol (1.94g) of the compound represented by formula (int II), 100mL of dichloromethane, 50mmol (8mL) of triethylamine, 25mmol (4mL) of pivaloyl chloride into a 250mL round bottom flask, stir at room temperature for 1h, and add 100mL of water After washing, the aqueous phase was extracted with 100 mL of dichloromethane, and the combined organic phase was washed with 250 mL of saturated sodium chloride solution, and dried with anhydrous sodium sulfate. After removing sodium sulfate, evaporating most of the dichloromethane, adding petroleum ether to make the product completely precipitate out, and filtering with suction to obtain 2.91 g of the compound shown in (int III), a white powdery solid, with a yield of 92%.

¹ H NMR (400MHz, CDCl ₃ , TMS) δ 7.64 (d, J = 8.0 Hz, 4H), 7.02 (s, 4H), 6.95 (dd, J = 8.4 Hz, J = 1.6 Hz, 4H), 6.70 (d,J=1.6Hz,4H),3.80(t,J=6.8Hz,4H),2.02-1.91(m,8H),1.24(s,36H),0.98(t,J=7.2Hz,12H) ；

¹³ C NMR(100MHz, CDCl ₃ )δ177.0, 139.4, 137.4, 133.9, 128.4, 125.8, 124.9, 47.1, 39.7, 28.2, 27.8, 13.0;

_{HRMS (-p ESI) Calc.for C 56} H 75 N 4 O 4 [MH] - 867.5794, Found 867.5804.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (int III).

Add 3mmol (2.5g) of the compound represented by formula (int III), 100mL of carbon disulfide, 48mmol (6.1g) of anhydrous aluminum trichloride, 72mmol (3.5mL) of elemental bromine into a 250mL round bottom flask, and stir vigorously for 24h at room temperature. Add 100 mL of dichloromethane, 100 mL of water and continue to stir for 10 min, the aqueous phase is extracted with 100 mL of dichloromethane, the organic phase is washed with a mixed solution of 200 mL of sodium chloride and sodium dithionite, and dried with anhydrous sodium sulfate. Remove the sodium sulfate, add 230-400 mesh silica gel, and spin dry for sample preparation. The stationary phase is 230-400 mesh silica gel, and the mobile phase ranges from petroleum ether: dichloromethane = 5: 5 to petroleum ether: dichloromethane: ethyl acetate = 5: 5:1. After column chromatography separation and purification, (int IV) The compound shown is 1.44 g, white solid, and the yield is 45%.

¹ H NMR (400MHz, CDCl ₃ , TMS) δ 8.32 (s, 2H), 7.94 (s, 2H), 7.53 (s, 2H), 7.29 (s, 2H), 6.41 (s, 2H), 5.90 ( s, 2H), 4.07-4.04 (m, 2H), 3.95-3.91 (m, 2H), 2.07-1.74 (m, 8H), 1.40 (s, 18H), 1.11 (s, 18H), 1.03 (t, J=6.8Hz, 12H);

¹³ C NMR (100MHz, CDCl ₃ , TMS) δ 177.0, 176.7, 139.3, 137.2, 136.3, 135.2, 135.0, 131.3, 129.0, 128.4, 126.7, 126.6, 124.1, 122.3, 46.5, 46.4, 40.0, 39.5, 27.7, 27.4 ,27.0,26.6,12.9,12.8;

_{HRMS (-p ESI) Calc.for C 56} H 71 N 4 O 4 Br 4 [MH] - 1183.2173, Found 1183.2185.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (int IV).

Add 2 mmol (2.39 g) of the compound represented by the formula (int IV) and 100 mL of sulfuric acid with a volume fraction of 0.5 to a 250 mL round bottom flask, and react at 150° C. for 48 hours with vigorous stirring, and then cool to room temperature. 80g sodium hydroxide is dissolved in 600mL water and cooled to room temperature. The cooled reaction system was poured into an alkali, extracted three times with 700 mL of ethyl acetate while it was hot, and the combined organic phase was washed with 250 mL of saturated sodium chloride solution, and dried with anhydrous sodium sulfate. After removing the sodium sulfate, evaporating most of the ethyl acetate, adding petroleum ether to make the product completely precipitate out, and filtering with suction to obtain 1.5 g of the compound shown in (VIIIa), a white powdery solid, with a yield of 90%.

¹ H NMR (400MHz, DMSO-d ₆ , TMS) δ 6.79 (s, 4H), 6.66 (b, 4H), 4.66 (b, 8H), 3.80 (t, J = 7.6 Hz, 4H), 1.87- 1.76(m,8H),0.87(t,J=7.2Hz,12H);

¹³ C NMR (400MHz, DMSO-d ₆ ) δ145.5, 128.4, 126.7, 122.5, 118.0, 113.7, 44.3, 27.7, 12.4;

_{HRMS (-p ESI) Calc.for C 36} H 39 N 4 Br 4 [MH] - 846.9873, Found 846.9869.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (VIIIa).

Example 5: Preparation of Compound (Xa)

Method one reaction formula is as follows:

The specific preparation method is: adding the compound represented by formula (IXa) (1 mmol, 1.68 g), tetratriphenylphosphine palladium (0.25 mmol, 292 mg), and potassium phosphate (6 mmol, 11.29 g) into a dry 25 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 100°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether:dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 501 mg of compound (Xa), a white powdery solid, and the yield is 46%.

Method 2 reaction formula is as follows:

The specific preparation method is: adding the compound represented by formula (IXa) (1 mmol, 1.68 g) and potassium phosphate (6 mmol, 11.29 g) into a dry 25 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 100°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 828 mg of compound (Xa), a white powdery solid, and the yield is 76%.

¹ H NMR(400MHz, Chloroform-d)δ7.20(s,4H), 6.84(s,4H), 4.67(t,J=8.1Hz,2H), 3.48(t,J=6.8Hz,2H), 2.43-2.33(m,8H), 1.45(t,J=7.1Hz,6H), 1.16(t,J=7.3Hz,6H).

HRMS(APCI)calcd for C ₄₀ H ₃₅ O ₂ 547.26425.Found 547.26440.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Xa).

Example 6: Preparation of compound (XIIa)

Method one reaction formula is as follows:

The specific preparation method is:

Add 0.3mmol (737mg) of the compound represented by formula (XIa), 0.15mmol (190mg) Pd(PPh ₃ ) ₄ and 1.8mmol K ₃ PO ₄ (410mg) into a 25mL reaction flask, and inject 10mL N,N- under an Ar atmosphere. Dimethylformamide, heated to 100°C and reacted for 24h. After cooling to room temperature, pour the system into 100 mL of water while stirring, extract the organic phase with dichloromethane (50 mL×3), dry with sodium sulfate, spin dry, and separate by column chromatography. The stationary phase is 230-400 mesh silica gel. The phase is dichloromethane: petroleum ether = 1:1, 52 mg of the compound shown in (XIIa) can be obtained, a white powdery solid, and the yield is 11%.

Method 2 reaction formula is as follows:

The specific preparation method is:

Put 0.3mmol (730mg) of the compound represented by formula (XIa) and 1.8mmol of Na ₂ CO ₃ (190mg) in a 25mL reaction flask, add 10mL of N,N-dimethylformamide, and add 15μL of water, and heat to 60 ℃ and react for 6h. After cooling to room temperature, pour the system into 100 mL of water while stirring, extract the organic phase with dichloromethane (50 mL×3), dry with sodium sulfate, spin dry and separate by column chromatography. The stationary phase is 230-400 mesh silica gel. The phase is dichloromethane: petroleum ether = 1:1, 103 mg of the compound shown in (XIIa) can be obtained, a white powdery solid, and the yield is 21%.

¹ H NMR (500MHz, CDCl ₃ ) δ7.31 (s, 6H), 6.99 (s, 6H), 4.65 (t, J = 7.9 Hz, 3H), 3.83 (t, J = 6.6 Hz, 3H), 2.23 -2.11(m,6H),1.82-1.71(m,6H),1.00(t,J=7.2Hz,9H),0.92(t,J=7.3Hz,9H).

¹³ C NMR (125MHz, CDCl ₃ ) δ 150.7, 146.0, 131.5, 127.7, 125.8, 118.7 (q, J = 320.6 Hz), 110.1, 41.2, 36.4, 33.8, 29.2, 12.3, 10.8.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (XIIa).

Example 7: Preparation of compound (IIIa)

Method one reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xa) (1 mmol, 1.10 mg), tetrakistriphenylphosphine palladium (0.25 mmol, 289 mg), and potassium phosphate (6 mmol, 1272 mg) into a dry 25 mL SCHLECK tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, 50 mL of dichloromethane was added, the solid insolubles were removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether:dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 16 mg of the compound shown in (IIIa), a white powdery solid, and a yield of 3%.

Method 2 reaction formula is as follows:

The specific preparation method is:

Put 1mmol (1.10g) of the compound represented by formula (Xa) and 1.8mmol K ₂ CO ₃ (190mg) in a 25mL reaction flask, add 10mL N,N-dimethylformamide, and add 15μL of water, and heat to 60 ℃ and react for 6h. After cooling to room temperature, pour the system into 100 mL of water while stirring, extract the organic phase with dichloromethane (50 mL×3), dry with sodium sulfate, spin dry, and separate by column chromatography. The stationary phase is 230-400 mesh silica gel. The phase is dichloromethane: petroleum ether = 1:1, 63 mg of the compound shown in (IIIa) can be obtained, a white powdery solid, and the yield is 12%.

Method 3 reaction formula is as follows:

The specific preparation method is:

Put 1mmol (600mg) of the compound represented by formula (XIIIa), 4.4mmol N-phenylbis(trifluoromethanesulfonyl)imide (1.57g) and 8mmol K ₂ CO ₃ (1.10g) into a 25mL reaction flask, Add 10 mL of N,N-dimethylformamide, stir at room temperature for 6 hours, and then heat to 100° C. to continue the reaction for 12 hours. After cooling to room temperature, the system was poured into 100 mL of water with stirring, extracted with dichloromethane (50 mL×3), the organic phase was dried with sodium sulfate, spin-dried and separated by column chromatography. The stationary phase was 230-400 mesh silica gel, mobile The phase is dichloromethane: petroleum ether = 2:1. After the solid obtained by column chromatography is washed with methanol, 12 mg of the compound shown in (IIIa) can be obtained, a white powdery solid, and the yield is 2%. The product is X-ray single crystal diffraction The figure is shown in Figure 9.

¹ H NMR (500MHz, CDCl ₃ ) δ 6.95 (s, 4H), 6.49 (s, 4H), 3.59 (t, J = 7.3 Hz, 4H), 2.05-1.96 (m, 8H), 1.26 (t, J = 7.3Hz, 12H). (Figure 7)

¹³ C NMR (125MHz, CDCl ₃ ) δ162.6, 135.5, 118.8, 114.2, 40.8, 18.8, 12.6. (Figure 8)

It can be seen from the above that the above-mentioned compound has the correct structure and is a compound represented by formula (IIIa).

Example 8: Preparation of compound (VIa)

Method one reaction formula is as follows:

The specific preparation method is:

Add 0.06 mmol (107 mg) of the compound represented by formula (XIIa), 0.45 mmol K ₃ PO ₄ (96 mg), and 5 mL of N,N-dimethylformamide into a 25 mL reaction flask, heat to 120° C. and react for 10 hours. After cooling to room temperature, the system was poured into 50 mL of water while stirring, and the organic phase was extracted with dichloromethane (50 mL×3) and dried with sodium sulfate, spin-dried and separated by column chromatography. The stationary phase was 230-400 mesh silica gel. The phase is dichloromethane: petroleum ether = 2:1, 33 mg of the compound shown in (VIa) can be obtained, a white powdery solid, and the yield is 64%.

Method 2 reaction formula is as follows:

The specific preparation method is:

Put 0.36mmol (910mg) of the compound represented by formula (XIa) and 6.0mmol K ₃ PO ₄ (190mg) in a 25mL reaction flask, add 15mL N,N-dimethylformamide, and add 42μL of water, and heat to 120 ℃ and react for 24h. After cooling to room temperature, pour the system into 100 mL of water while stirring, extract the organic phase with dichloromethane (50 mL×3), dry with sodium sulfate, spin dry, and separate by column chromatography. The stationary phase is 230-400 mesh silica gel. The phase is dichloromethane: petroleum ether = 2:1, 18 mg of the compound shown in (VIa) can be obtained, a white powdery solid, and the yield is 6%.

Method 3 reaction formula is as follows:

The specific preparation method is:

Put 1mmol (901mg) of the compound represented by formula (XIVa), 6.3mmol N-phenylbis(trifluoromethanesulfonyl)imide (2.25g) and 12mmol K ₂ CO ₃ (1.66g) into a 25mL reaction flask, Add 10 mL of N,N-dimethylformamide, stir at room temperature for 6 hours, and then heat to 100° C. to continue the reaction for 12 hours. After cooling to room temperature, pour the system into 100 mL of water while stirring, extract the organic phase with dichloromethane (50 mL×3), dry with sodium sulfate, spin dry, and separate by column chromatography. The stationary phase is 230-400 mesh silica gel. The phase is dichloromethane: petroleum ether = 2:1. After the solid obtained by column chromatography is washed with methanol, 89 mg of the compound shown in (VIa) can be obtained, a white powdery solid, the yield is 11%, and the product is X-ray single crystal diffraction The figure is shown in Figure 18.

¹ H NMR (500MHz, CDCl ₃ ) δ 6.85 (s, 6H), 6.74 (s, 6H), 3.52 (t, J = 6.6 Hz, 3H), 3.34 (t, J = 7.6 Hz, 3H), 2.13 -2.02(m,6H),1.75-1.67(m,6H),1.32(t,J=7.3Hz,9H),0.93(t,J=7.3Hz,9H). (Figure 16)

¹³ C NMR (125MHz, CDCl ₃ ) δ157.1, 154.4, 128.6, 126.6, 122.8, 108.7, 45.5, 38.6, 29.4, 19.2, 13.2, 12.3. (Figure 17)

HRMS(APCI)calcd for C ₄₀ H ₃₅ O ₂ 547.26425.Found 547.26440.

Anal.cacld for C ₅₄ H ₄₈ O ₆ ·0.5C ₅ H ₁₂ : C 81.86, H 6.57; found C 82.03, H 6.46.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (VIa).

Example 9: Preparation of compound (XVa)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-toluidine (2mmol, 214mg), three (dibenzylideneacetone) two palladium (0) chloroform complexes (0.1mmol, 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 8 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 755 mg of the compound shown in (XVa), a white powdery solid, and the yield is 84%.

¹ H NMR(400MHz,CDCl ₃ )δ7.28(d,J=8.6Hz,2H),7.19(s,2H),7.13(d,J=8.4Hz,2H),6.78(s,2H),6.77 (s, 2H), 6.59 (s, 2H), 4.66 (t, J = 8.1 Hz, 1H), 3.72 (t, J = 7.5 Hz, 1H), 3.43 (t, J = 6.8 Hz, 2H), 2.33 (s,3H),2.22-2.31(m,4H),2.01-2.06(m,2H),1.90-1.97(m,2H),1.30(t,J=7.3Hz,9H),1.14(t,J ＝7.3Hz, 3H).

¹⁹ F NMR (376MHz, CDCl ₃ ) δ-72.71.

¹³ C NMR (101MHz, CDCl ₃ ) δ 159.1, 156.1, 147.7, 143.7, 140.0, 139.3, 133.7, 133.6, 132.0, 130.0, 128.9, 119.4, 118.8 (J = 319.4 Hz), 118.3, 117.8, 113.8, 111.3, 43.6 ,39.6,39.4,21.6,20.6,19.2,18.6,12.8,12.5,12.3.

HRMS(APCI)calcd.for C ₄₅ H ₄₀ F ₆ NO ₈ S ₂ ⁺ :[M+H] ⁺ 900.2094,Found 900.2086.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (XVa).

Example 10: Preparation of compound (XVb)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-fluoroaniline (2mmol, 222mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.1mmol, 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 8 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 560 mg of the compound shown in (XVb), a white powdery solid, and the yield is 62%.

¹ H NMR(400MHz,CDCl ₃ )δ7.31(t,J=4.5Hz,2H),7.16(s,2H),7.02(t,J=8.6Hz,2H),6.79(s,2H),6.78 (s, 2H), 6.60 (s, 2H), 4.67 (t, J = 8.1 Hz, 1H), 3.73 (t, J = 7.5 Hz, 1H), 3.43 (t, J = 6.8 Hz, 2H), 2.34 –2.21(m,4H),2.08-2.01(m,2H),1.97-1.91(m,2H),1.33-1.28(m,9H),1.14(t,J=7.3Hz,3H).

¹⁹ F NMR (376MHz, CDCl ₃ ) δ-72.71, -125.35.

¹³ C NMR (101MHz, CDCl ₃ ) δ 159.0, 156.7 (J=237.4Hz), 156.2, 147.5, 143.7, 140.2, 138.1, 134.0, 133.6, 132.1, 119.5, 118.8 (J=319.4Hz), 118.5, 117.6, 116.1 (J=22.0Hz), 114.6 (J=7.7Hz), 111.3, 43.7, 39.6, 39.4, 21.6, 19.2, 18.6, 12.8, 12.4, 12.3.

HRMS(APCI)calcd.for C ₄₄ H ₃₇ F ₇ NO ₈ S ₂ ⁺ :[M+H] ⁺ 904.1843,Found 904.1832.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (XVb).

Example 11: Preparation of compound (XVc)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-cyanoaniline (2mmol, 236mg), tris (dibenzylideneacetone) two palladium (0) chloroform complex (0.1mmol) to the dry 100mL reaction tube , 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 8 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=1:1, and column chromatography is performed to separate and purify the compound to obtain 546 mg of compound (XVc), a white powdery solid, and a yield of 61%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.58 (d, J = 8.9 Hz, 2H), 7.34 (d, J = 8.9 Hz, 2H), 7.08 (s, 2H), 6.83 (s, 2H), 6.80 (s, 2H), 6.60 (s, 2H), 4.67 (t, J = 8.1 Hz, 1H), 3.74 (t, J = 7.5 Hz, 1H), 3.44 (t, J = 6.7 Hz, 2H), 2.31 -2.23(m,4H), 2.19-2.00(m,2H),1.97-1.90(m,2H), 1.30(t,J=7.2Hz,9H), 1.14(t,J=7.2Hz,3H).

¹⁹ F NMR (376MHz, CDCl ₃ ) δ-72.68.

¹³ C NMR (101MHz, CDCl ₃ ) δ 158.8, 156.4, 145.9, 145.2, 143.8, 141.2, 135.2, 134.0, 133.4, 132.2, 119.9, 119.5, 118.9, 118.8 (J = 319.2 Hz), 118.4, 113.4, 111.4, 101.4 ,43.7,39.7,39.4,21.6,19.2,18.6,12.8,12.4,12.3.

HRMS(APCI)calcd.for C ₄₅ H ₃₇ F ₆ N ₂ O ₈ S ₂ ⁺ :[M+H] ⁺ 911.1890,Found 911.1875.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (XVc).

Example 12: Preparation of compound (XVd)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), 2-naphthylamine (2mmol, 286mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.1mmol) to the dry 100mL reaction tube , 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 8 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, and the mobile phase is petroleum ether: dichloromethane=2.5:1. After column chromatography separation and purification, 692 mg of the compound shown in (XVd) can be obtained, a white powdery solid, and the yield is 74%.

¹ H NMR (400MHz, CDCl ₃ ) δ 8.20 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 5.3 Hz, 1H), 7.92 (d, J = 5.5 Hz, 1H), 7.75–7.62 (m,1H),7.57–7.49(m,1H),7.46(d,J=7.3Hz,1H),7.45–7.37(m,1H),6.86(s,2H),6.84(s,2H), 6.79 (s, 2H), 6.61 (s, 2H), 4.69 (t, J = 8.1 Hz, 1H), 3.94 (t, J = 7.4 Hz, 1H), 3.46 (t, J = 6.8 Hz, 2H), 2.54-2.47 (m, 2H), 2.30-2.22 (m, 2H), 2.11-2.04 (m, 2H), 1.99-1.92 (m, 2H), 1.45 (t, J = 7.3 Hz, 3H), 1.33 ( t,J=7.3Hz,6H),1.14(t,J=7.3Hz,3H).

¹⁹ F NMR (376MHz, CDCl ₃ ) δ-72.54.

¹³ C NMR (101MHz, CDCl ₃ ) δ 159.8, 156.8, 151.7, 143.7, 136.9, 135.5, 134.6, 133.8, 131.9, 131.8, 131.6, 128.6, 127.7, 126.5, 126.3, 125.1, 124.8, 124.2, 119.4, 118.8 (J ＝319.5HZ),117.7,113.6,111.2,43.2,39.7,39.2,22.1,19.4,19.1,12.9,12.6,12.3.

HRMS(APCI)calcd.for C ₄₈ H ₄₀ F ₆ NO ₈ S ₂ ⁺ :[M+H] ⁺ 936.2094,Found 936.2083.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (XVd).

Example 13: Preparation of compound (XVe)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), benzylamine (2mmol, 214mg), tris(dibenzylideneacetone), two palladium (0) chloroform complex (0.1mmol, 103.5mg) into the dry 100mL reaction tube. mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 8 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 512 mg of the compound shown in (XVe), a white powdery solid, and a yield of 57%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.56 (d, J = 7.2Hz, 2H), 7.36 (t, J = 7.5Hz, 2H), 7.31-7.26 (m, 1H), 6.86 (s, 2H) , 6.74 (s, 2H), 6.54 (s, 4H), 4.66 (t, J = 8.1 Hz, 1H), 4.59 (s, 2H), 3.70 (t, J = 7.5 Hz, 1H), 3.39 (t, J=6.9Hz,2H),2.43-2.36(m,2H),2.26-2.22(m,2H),2.07–1.95(m,2H),1.94-1.83(m,2H),1.37(t,J= 7.3Hz, 3H), 1.27 (t, J = 7.3Hz, 6H), 1.12 (t, J = 7.3Hz, 3H).

¹⁹ F NMR (376MHz, CDCl ₃ ) δ-72.64.

¹³ C NMR (101MHz, CDCl ₃ ) δ 159.5, 156.7, 153.0, 143.6, 137.2, 134.8, 134.2, 131.8, 131.1, 128.8, 128.2, 127.6, 119.3, 118.8 (J = 319.4 Hz), 117.8, 111.2, 110.6, 49.6 ,42.9,39.4,39.2,21.8,19.3,18.7,12.8,12.6,12.3.

HRMS(APCI)calcd.for C ₄₅ H ₄₀ F ₆ NO ₈ S ₂ ⁺ :[M+H] ⁺ 900.2094,Found 900.2081.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (XVe).

Example 14: Preparation of compound (XVf)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xc) (1mmol, 1316mg), p-toluidine (2mmol, 214mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.1mmol, 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 8 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, and the mobile phase is petroleum ether: dichloromethane=3.5:1. After column chromatography separation and purification, 786 mg of the compound represented by (XVf) can be obtained, a white powdery solid, and the yield is 70%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.28 (d, J = 8.7Hz, 2H), 7.18 (s, 2H), 7.13 (d, J = 8.2 Hz, 2H), 6.75 (s, 4H), 6.58 (s, 2H), 4.73 (t, J = 8.0 Hz, 1H), 3.78 (t, J = 7.6 Hz, 1H), 3.49 (t, J = 6.6 Hz, 2H), 2.32 (s, 3H), 2.26 -2.17(m,4H),1.84-1.96(m,4H),1.57-1.71(m,12H),1.33-1.47(m,20H),0.99(t,J=7.1Hz,6H),0.89-0.96 (m,6H).

¹⁹ F NMR (376MHz, CDCl ₃ ) δ-72.78.

¹³ C NMR (101MHz, CDCl ₃ ) δ 159.0, 156.1, 147.6, 143.6, 140.1, 139.3, 133.85, 133.77, 132.2, 130.0, 128.9,, 119.6, 118.8 (J = 319.4 Hz), 118.5, 117.7, 113.8, 111.2, 41.8, 37.7, 32.0, 31.8, 30.0, 29.9, 29.5, 28.5, 27.9, 27.8, 26.1,25.5, 22.9, 22.85, 22.76, 20.6, 14.3, 14.2.

HRMS(APCI)calcd.for C ₆₁ H ₇₂ F ₆ NO ₈ S ₂ ⁺ :[M+H] ⁺ 1124.4598,Found 1124.4583.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (XVf).

Example 15: Preparation of compound (IVa)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-toluidine (4mmol, 428mg), three (dibenzylideneacetone) two palladium (0) chloroform complexes (0.2mmol, 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed for separation and purification to obtain 360 mg of the compound shown in (IVa), a white powdery solid, and the yield is 51%.

The specific preparation method two is:

Add the compound represented by formula (XVa) (1mmol, 899mg), p-toluidine (2mmol, 214mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.1mmol, 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is carried out to separate and purify. 423.6mg of the compound shown in (IVa) can be obtained, a white powdery solid, and the yield is 60%. The X-ray single crystal diffraction pattern of the product is shown in Figure 12.

¹ H NMR(400MHz,CDCl ₃ )δ7.31(s,4H), 7.18(d,J=7.3Hz,4H), 7.07(d,J=8.2Hz,4H), 6.55(s,4H), 3.56 (t,J=7.1Hz,2H),3.44-3.49(m,2H),2.29(s,6H),2.02-2.09(m,8H),1.30(t,J=7.3Hz,6H),1.23( t,J=7.3Hz,6H). (Figure 10)

¹³ C NMR (101MHz, CDCl ₃ ) δ 161.5, 147.1, 139.9, 139.5, 136.0, 129.9, 128.3, 118.5, 118.4, 113.3, 77.5, 77.2, 76.8, 43.2, 40.9, 20.6, 18.9, 18.7, 12.6. 11)

HRMS(APCI)calcd.for C ₅₀ H ₄₇ N ₂ O ₂ ⁺ :[M+H] ⁺ 707.3632,Found 707.3619.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (IVa).

Example 16: Preparation of compound (IVb)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-fluoroaniline (4mmol, 444mg), tris (dibenzylideneacetone) two palladium (0) chloroform complex (0.2mmol, 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 414 mg of the compound shown in (IVb), a white powdery solid, and the yield is 58%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.31 (s, 4H), 7.19-7.23 (m, 4H), 6.94-6.98 (m, 4H), 6.57 (s, 4H), 3.57 (t, J = 7.1 Hz, 2H), 3.47 (t, J = 7.3 Hz, 2H), 2.03-2.10 (m, 8H), 1.30 (t, J = 7.3 Hz, 6H), 1.23-1.26 (m, 6H).

¹³ C NMR (101MHz, CDCl ₃ ) δ161.5, 156.5 (J=236.5Hz), 147.0, 139.6, 138.7, 136.2, 118.7, 118.2, 115.8 (J=21.9Hz), 114.2 (J=7.6Hz), 43.2, 40.9 ,18.8,18.7,12.6.

HRMS(APCI)calcd.for C ₄₈ H ₄₁ F ₂ N ₂ O ₂ ⁺ :[M+H] ⁺ 715.3131,found 715.3132.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (IVb).

Example 17: Preparation of compound (IVc)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), 1-naphthylamine (4mmol, 572mg), three (dibenzylideneacetone) two palladium (0) chloroform complexes (0.2mmol) to the dry 100mL reaction tube , 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane = 3:1, and column chromatography is performed to separate and purify the compound to obtain 233.4 mg of compound (IVc), a white powdery solid, and the yield is 30%.

The specific preparation method two is:

Add the compound represented by formula (XVd) (1mmol, 935mg), 1-naphthylamine (2mmol, 286mg), tris (dibenzylideneacetone) two palladium (0) chloroform complex (0.1mmol) to the dry 100mL reaction tube , 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane = 3:1, and column chromatography is performed to separate and purify the compound to obtain 482.4 mg of compound (IVc), a white powdery solid, with a yield of 62%.

¹ H NMR (400MHz, CDCl ₃ ) δ 8.37 (d, J = 8.2 Hz, 2H), 7.98 (t, J = 4.6 Hz, 2H), 7.94 (d, J = 7.8 Hz, 2H), 7.85 (d ,J=5.0Hz,4H),7.51(t,J=7.1Hz,2H),7.45(t,J=7.8Hz,2H),7.16(s,4H),6.62(s,4H),3.69(t ,J=8.0Hz,2H), 3.64(t,J=7.8Hz,2H),2.25-2.32(m,4H),2.05-2.13(m,4H),1.39(t,J=7.3Hz,6H) ,1.32(t,J=7.3Hz,6H).

¹³ C NMR ( _{101MHz, CDCl 3} ) δ 163.0, 150.2, 137.6, 135.7, 135.0, 133.1, 131.8, 128.4, 127.3, 126.6, 126.4, 125.0, 124.8, 124.1, 117.9, 113.7, 76.8, 42.8, 40.8, 19.3, 18.9 ,12.9,12.8.

HRMS(APCI)calcd.for C ₅₆ H ₄₇ N ₂ O ₂ ⁺ :[M+H] ⁺ 779.3632,found 779.3630.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (IVc).

Example 18: Preparation of compound (IVd)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (Xc) (1mmol, 1316mg), p-toluidine (4mmol, 428mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.2mmol, 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 567.3 mg of compound (IVd), a white powdery solid, and a yield of 61%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.30 (s, 4H), 7.18 (d, J = 8.7 Hz, 4H), 7.07 (d, J = 8.7 Hz, 4H), 6.53 (s, 4H), 3.64 (t,J=7.1Hz,2H),3.52(t,J=7.3Hz,2H),2.29(s,6H),2.00-2.02(m,8H),1.51-1.69(m,16H),1.36- 1.41(m,16H),0.92-0.98(m,12H).

¹³ C NMR ( _{101MHz, CDCl 3} ) δ 161.5, 147.0, 139.9, 139.6, 136.2, 129.9, 128.3, 118.6, 118.3, 113.3, 41.4, 39.1, 38.9, 32.1, 32.1, 30.0, 28.0, 25.8, 25.5, 22.9, 20.6 , 14.3.

HRMS(APCI)calcd.for C ₆₆ H ₇₉ N ₂ O ₂ ⁺ :[M+H] ⁺ 931.6136,Found 931.6124.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (IVd).

Example 19: Preparation of compound (IVe)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (XVa) (1mmol, 899mg), 2-naphthylamine (2mmol, 286mg), tris (dibenzylideneacetone) two palladium (0) chloroform complex (0.1mmol) to the dry 100mL reaction tube , 103.5mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.4mmol, 231.6mg), potassium phosphate (6mmol, 1272mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 371 mg of compound (IVe), a white powdery solid, with a yield of 50%.

¹ H NMR(400MHz,CDCl ₃ )δ7.74(d,J=6.4Hz,1H), 7.72(d,J=4.6Hz,1H), 7.61(d,J=8.2Hz,1H), 7.55(d ,J=2.7Hz,1H),7.53(s,1H),7.37-7.41(m,1H),7.39(s,2H),7.35(d,J=5.5Hz,2H),7.24-7.28(m, 1H), 7.19 (d, J = 8.2 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 6.61 (s, 2H), 6.59 (s, 2H), 3.60 (t, J = 7.1 Hz, 2H), 3.54 (t, J = 7.3 Hz, 1H), 3.48 (t, J = 7.6 Hz, 1H), 2.28 (s, 3H), 2.06-2.12 (m, 8H), 1.32 (t, J = 7.3 Hz,6H),1.25(t,J=7.1Hz,6H).

¹³ C NMR ( _{101MHz, CDCl 3} ) δ161.6, 161.5, 147.1, 146.8, 140.1, 140.0, 139.9, 139.5, 136.5, 136.0, 134.9, 129.9, 129.2, 128.3, 128.1, 127.7, 126.7, 126.6, 123.0, 118.9, 118.8 ,118.6,118.4,116.0,113.3,107.2,43.3,43.2,41.0,20.5,18.9,18.7,12.6.

HRMS(APCI)calcd.for C ₅₃ H ₄₇ N ₂ O ₂ ⁺ :[M+H] ⁺ 743.3632,Found 743.3628.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (IVe).

Example 20: Preparation of compound (VIIa)

The reaction formula is as follows:

The specific preparation method is:

Add the compound represented by formula (XIIa) (1mmol, 1638mg), p-anisidine (6mmol, 738mg), tris (dibenzylideneacetone) two palladium (0) chloroform complex (0.3 mmol, 310.5 mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (1.2 mmol, 694.8 mg), potassium phosphate (18 mmol, 3816 mg). The air in the reaction tube was evacuated three times to replace it with argon, and 20 mL of dry xylene was added to the system. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is dichloromethane, and the column chromatography is performed to separate and purify the compound to obtain 221.4 mg of the compound shown in (VIIa), a white powdery solid, and the yield is 20%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.39 (d, J = 8.8Hz, 6H), 7.03 (d, J = 8.8Hz, 6H), 6.74 (s, 6H), 6.71 (s, 6H), 3.32 -3.27(m,6H),2.24-2.18(m,6H),1.74-1.62(m,6H),1.33(t,J=7.2Hz,9H),0.93(t,J=7.3Hz,9H).

HRMS(APCI)calcd.for C ₇₅ H ₇₀ N ₃ O ₆ ⁺ :[M+H] ⁺ 1108.5259,Found 1108.5254.

It can be seen from the above that the above compound has the correct structure and is a compound represented by formula (VIIa).

Example 21: Preparation of Compound (Va)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-toluidine (1mmol, 107mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.2mmol, 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, 20 mL of dry xylene was added to the system, and then H ₂ O (1 mmol, 18 μL) was injected. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 283.8 mg of the compound shown in (Va), a white powdery solid, and the yield is 46%.

The specific preparation method two is:

Add the compound represented by formula (XVa) (1 mmol, 899 mg), tetrakistriphenylphosphine palladium (0.25 mmol, 289 mg), and potassium phosphate (6 mmol, 1272 mg) into a dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 493.6 mg of compound (Va), a white powdery solid, and the yield is 80%.

The specific preparation method three is:

Add the compound represented by formula (XVa) (1 mmol, 899 mg) and potassium phosphate (6 mmol, 1272 mg) into a dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 370.2 mg of compound (Va), a white powdery solid, and a yield of 60%. The X-ray single crystal diffraction pattern of the product is shown in Figure 15.

¹ H NMR(400MHz,CDCl ₃ )δ7.43(s,2H), 7.25(d,J=9.2Hz,2H), 7.13(d,J=8.3Hz,2H), 6.85(s,2H), 6.55 (s, 2H), 6.52 (s, 2H), 3.58 (t, J = 6.9 Hz, 3H), 3.47 (t, J = 7.3 Hz, 1H), 2.33 (s, 3H), 2.12-1.94 (m, 8H), 1.27(dt, J=19.7, 7.2Hz, 12H). (Figure 13)

¹³ C NMR ( _{101MHz, CDCl 3} ) δ 162.8, 162.2, 161.8, 146.9, 139.8, 139.2, 135.9, 135.6, 135.5, 129.9, 128.4, 118.8, 118.6, 118.2, 118.2, 114.1, 113.4, 43.2, 40.8, 40.7, 20.6 , 18.82, 18.75, 18.7, 12.7, 12.62, 12.60. (Figure 14)

HRMS(APCI)calcd.for C ₄₃ H ₄₀ NO ₃ ⁺ :[M+H] ⁺ 618.3003,Found 618.2990.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Va).

Example 22: Preparation of compound (Vb)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-fluoroaniline (1mmol, 111mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.2mmol, 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, 20 mL of dry xylene was added to the system, and then H ₂ O (1 mmol, 18 μL) was injected. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 236 mg of the compound shown in (Vb), a white powdery solid, and the yield is 38%.

The specific preparation method two is:

Into a dry 100 mL reaction tube was added the compound represented by formula (XVb) (1 mmol, 903 mg), tetrakistriphenylphosphine palladium (0.25 mmol, 289 mg), and potassium phosphate (6 mmol, 1272 mg). The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 509.2 mg of the compound shown in (Vb), a white powdery solid, and the yield is 82%.

The specific preparation method three is:

Add the compound represented by formula (XVb) (1 mmol, 903 mg) and potassium phosphate (6 mmol, 1272 mg) into a dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed for separation and purification to obtain 496.8 mg of the compound shown in (Vb), a white powdery solid, and the yield is 80%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.37 (s, 2H), 7.25-7.20 (m, 2H), 6.99 (t, J = 8.7 Hz, 2H), 6.87 (s, 2H), 6.54 (s, 2H),6.52(s,2H),3.58(q,J=7.5Hz,3H), 3.46(t,J=7.3Hz,1H),2.07–1.99(m,8H),1.30–1.23(m,12H ).

¹³ C NMR (101MHz, CDCl ₃ ) δ 162.8, 162.2, 161.9, 156.5 (J=236.6Hz), 146.8, 139.5, 138.7, 136.2, 135.7, 135.4, 118.8, 118.7, 118.2, 115.9 (J=22.3Hz), 114.2 (J=5.7Hz), 114.1, 43.2, 40.8, 40.7, 18.8, 18.74, 18.68, 12.6.

HRMS(APCI)calcd.for C ₄₂ H ₃₇ FNO ₃ ⁺ :[M+H] ⁺ 622.2752,found 622.2753.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Vb).

Example 23: Preparation of compound (Vc)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-cyanoaniline (1mmol, 118mg), three (dibenzylideneacetone) two palladium (0) chloroform complex (0.2mmol) to the dry 100mL reaction tube , 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, 20 mL of dry xylene was added to the system, and then H ₂ O (1 mmol, 18 μL) was injected. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and the column chromatography is performed to separate and purify the compound to obtain 219.8 mg of compound (Vc), a white powdery solid, and the yield is 35%.

The specific preparation method two is:

Into a dry 100 mL reaction tube was added the compound represented by formula (XVc) (1 mmol, 910 mg), tetrakistriphenylphosphine palladium (0.25 mmol, 289 mg), and potassium phosphate (6 mmol, 1272 mg). The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=1:1, and column chromatography is performed to separate and purify the compound to obtain 383 mg of compound (Va), a white powdery solid, and a yield of 61%.

The specific preparation method three is:

Add the compound represented by formula (XVc) (1 mmol, 910 mg) and potassium phosphate (6 mmol, 1272 mg) into a dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=1:1, and column chromatography is performed to separate and purify the compound to obtain 314 mg of the compound shown in (Va), a white powdery solid, and the yield is 50%.

¹ H NMR (400MHz, CDCl ₃ ) δ 7.54 (d, J = 8.9 Hz, 2H), 7.28 (s, 2H), 7.24 (d, J = 8.9 Hz, 2H), 6.88 (s, 2H), 6.56 (s, 2H), 6.55 (s, 2H), 3.59 (t, J = 7.0 Hz, 3H), 3.48 (t, J = 7.5 Hz, 1H), 2.09-1.98 (m, 8H), 1.29-1.22 ( m,12H).

¹³ C NMR ( _{101MHz, CDCl 3} ) δ 162.9, 162.1, 145.7, 145.2, 140.2, 137.4, 135.8, 135.2, 134.0, 119.2, 119.0, 118.8, 118.6, 114.1, 113.2, 113.0, 100.9, 43.2, 40.9, 40.7, 18.8 , 18.74, 18.66, 12.6.

HRMS(APCI)calcd.for C ₄₃ H ₃₇ N ₂ O ₃ ⁺ :[M+H] ⁺ 629.2799,found 629.2797.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Vc).

Example 24: Preparation of compound (Vd)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), 1-naphthylamine (1mmol, 143mg), three (dibenzylideneacetone) two palladium (0) chloroform complexes (0.2mmol) to the dry 100mL reaction tube , 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, 20 mL of dry xylene was added to the system, and then H ₂ O (1 mmol, 18 μL) was injected. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=2:1, and column chromatography is performed for separation and purification to obtain 261.2 mg of compound (Vd), a white powdery solid, and a yield of 40%.

The specific preparation method two is:

Into a dry 100 mL reaction tube were added the compound represented by formula (XVd) (1 mmol, 935 mg), tetrakistriphenylphosphine palladium (0.25 mmol, 289 mg), and potassium phosphate (6 mmol, 1272 mg). The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane = 2:1, and column chromatography is performed for separation and purification to obtain 483.2 mg of the compound shown in (Vd), a white powdery solid, and the yield is 74%.

The specific preparation method three is:

Add the compound represented by formula (XVd) (1 mmol, 935 mg) and potassium phosphate (6 mmol, 1272 mg) into a dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane = 2:1, and column chromatography is performed to separate and purify the compound to obtain 528.3 mg of the compound represented by (Vd), a white powdery solid, and the yield is 81%.

¹ H NMR (400MHz, CDCl ₃ ) δ 8.21 (d, J = 8.7 Hz, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.84 (d ,J=8.2Hz,1H),7.71(t,J=7.8Hz,1H),7.49(t,J=7.3Hz,1H),7.42(t,J=7.6Hz,1H),7.20(s,2H ), 6.96 (s, 2H), 6.56 (s, 4H), 3.74 (t, J = 7.1 Hz, 1H), 3.56-3.63 (m, 3H), 2.17-2.24 (m, 2H), 2.02-2.09 ( m, 6H), 1.36 (t, J = 7.3 Hz, 3H), 1.27-1.31 (m, 9H).

¹³ C NMR ( _{101MHz, CDCl 3} ) δ 162.9, 162.3, 162.1, 150.7, 137.9, 136.2, 135.7, 135.1, 134.6, 134.3, 130.4, 128.5, 126.34, 126.26, 125.9, 125.2, 124.8, 122.6, 118.6, 118.2, 114.8 ,114.0,43.0,40.8,40.6,19.2,18.8,12.8,12.7,12.6.

HRMS(APCI)calcd.for C ₄₆ H ₄₀ NO ₃ ⁺ :[M+H] ⁺ 654.3003,found 654.3001.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Vd).

Example 25: Preparation of compound (Ve)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), benzylamine (4mmol, 107mg), three (dibenzylideneacetone) two palladium (0) chloroform complexes (0.2mmol, 207mg) to the dry 100mL reaction tube ), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, 20 mL of dry xylene was added to the system, and then H ₂ O (1 mmol, 18 μL) was injected. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 320.8 mg of the compound represented by (Ve), a white powdery solid, and the yield is 52%.

The specific preparation method two is:

Into a dry 100 mL reaction tube were added the compound represented by formula (XVe) (1 mmol, 899 mg), tetrakistriphenylphosphine palladium (0.25 mmol, 289 mg), and potassium phosphate (6 mmol, 1272 mg). The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 530.6 mg of compound (Ve), a white powdery solid, and a yield of 86%.

The specific preparation method three is:

The compound represented by formula (XVe) (1 mmol, 899 mg) and potassium phosphate (6 mmol, 1272 mg) were added to the dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, and the mobile phase is petroleum ether: dichloromethane=3.5:1. After column chromatography separation and purification, 468.9 mg of the compound represented by (Ve) can be obtained, a white powdery solid, and the yield is 76%.

¹ H NMR(400MHz, CDCl ₃ )δ7.55(d,J=7.4Hz,2H), 7.32(t,J=7.5Hz,2H), 7.22(t,J=7.3Hz,1H), 6.92(s , 2H), 6.83 (s, 2H), 6.49 (s, 2H), 6.46 (s, 2H), 4.73 (s, 2H), 3.55 (t, J = 7.4 Hz, 3H), 3.45 (t, J = 7.3Hz, 1H), 2.16-2.09 (m, 2H), 2.04-1.97 (m, 6H), 1.30-1.24 (m, 12H).

¹³ C NMR ( _{101MHz, CDCl 3} ) δ 162.8, 162.4, 162.1, 152.2, 137.4, 136.0, 135.2, 134.0, 133.4, 128.7, 128.3, 127.4, 118.4, 118.0, 113.9, 110.6, 50.1, 42.5, 40.6, 18.9, 18.7 , 12.8, 12.6.

HRMS(APCI)calcd.for C ₄₃ H ₄₀ NO ₃ ⁺ :[M+H] ⁺ 618.3003,found 618.3002.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Ve).

Example 26: Preparation of compound (Vf)

The reaction formula is as follows:

The specific preparation method one is:

Add the compound represented by formula (Xa) (1mmol, 1092mg), p-toluidine (1mmol, 107mg), three (dibenzylideneacetone) two palladium (0) chloroform complexes (0.2mmol, 207mg), 4,5-bisdiphenylphosphine-9.9-dimethylxanthene (0.8mmol, 463.2mg), potassium phosphate (12mmol, 2544mg). The air in the reaction tube was evacuated three times to replace it with argon, 20 mL of dry xylene was added to the system, and then H ₂ O (1 mmol, 18 μL) was injected. The system was heated at 150°C in an oil bath under magnetic stirring and reacted for 48 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 546.7 mg of compound (Vf), a white powdery solid, and the yield is 65%.

The specific preparation method two is:

Add the compound represented by formula (XVf) (1 mmol, 1123 mg), tetrakistriphenylphosphine palladium (0.25 mmol, 289 mg), and potassium phosphate (6 mmol, 1272 mg) into a dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 504.6 mg of the compound represented by (Vf), a white powdery solid, and the yield is 60%.

The specific preparation method three is:

Add the compound represented by formula (XVf) (1 mmol, 1123 mg) and potassium phosphate (6 mmol, 1272 mg) into a dry 100 mL reaction tube. The air in the reaction tube was evacuated three times to replace it with argon, and 10 mL of solvent N,N-dimethylformamide was added. The system was heated in an oil bath at 140°C under magnetic stirring and reacted for 20 hours. After cooling to room temperature, the solid insoluble matter was removed by suction filtration, the filtrate was washed with 50 mL of brine, the organic phase was dried, and 230-400 mesh silica gel was added, and the sample was spin-dried. The stationary phase is 230-400 mesh silica gel, the mobile phase is petroleum ether: dichloromethane=3.5:1, and column chromatography is performed to separate and purify the compound to obtain 530.5 mg of compound (Vf), a white powdery solid, and a yield of 63%.

¹ H NMR (400MHz, CDCl ₃ ) δ7.41 (s, 2H), 7.24 (d, J = 8.6Hz, 2H), 7.12 (d, J = 8.4Hz, 2H), 6.83 (s, 2H), 6.52 (s, 2H), 6.49 (s, 2H), 3.65 (t, J = 6.9 Hz, 3H), 3.53 (t, J = 7.3 Hz, 1H), 2.33 (s, 3H), 2.01-1.96 (m, 8H), 1.76-1.60 (m, 8H), 1.56 (s, 8H), 1.41--1.39 (m, 16H), 1.02-0.90 (m, 12H).

¹³ C NMR ( _{101MHz, CDCl 3} ) δ 162.7, 162.2, 161.7, 146.8, 139.7, 139.2, 136.0, 135.7, 135.6, 129.9, 128.4, 118.8, 118.6, 118.1, 114.1, 113.4, 41.1, 38.7, 38.6, 27.9, 27.8 ,27.7,21.2,21.1,20.6,14.7,14.6.

HRMS(APCI)calcd.for C ₅₉ H ₇₂ NO ₃ ⁺ :[M+H] ⁺ 842.5507,Found 842.5513.

It can be seen from the above that the above compound has a correct structure and is a compound represented by formula (Vf).

In the description of this specification, descriptions with reference to the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" etc. mean specific features described in conjunction with the embodiments or examples. , Structures, materials, or characteristics are included in at least one embodiment or example of the present disclosure. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials or characteristics can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine the different embodiments or examples and the features of the different embodiments or examples described in this specification without contradicting each other.

Although the embodiments of the present disclosure have been shown and described above, it can be understood that the above-mentioned embodiments are exemplary and should not be construed as limiting the present disclosure. Those of ordinary skill in the art can comment on the foregoing within the scope of the present disclosure. The embodiment undergoes changes, modifications, substitutions, and modifications.

Claims (72)

1. A compound characterized in that the compound is a compound represented by formula (I) or a stereoisomer of a compound represented by formula (I),

   

   in,

   Ra is ^a hydrogen atom, optionally substituted C _1-12 alkyl, optionally substituted C _1-12 heteroalkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _5-24 cycloalkane Group, optionally substituted C _5-24 heterocyclyl or optionally substituted benzyl.
2. The compound of claim 1, wherein:

   Ra is ^a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 cycloalkyl, C _5-12 heterocycloalkyl, benzyl, or C _1-6 alkyl substituted benzyl.
3. The compound of claim 1, wherein:

   R ^a is a hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl , Benzyl, p-methylbenzyl, o-methylbenzyl or m-methylbenzyl.
4. The compound according to claim 1, characterized in that it has one of the following structures:

   
5. A compound characterized in that the compound is a compound represented by formula (II) or a stereoisomer of a compound represented by formula (II),

   

   in,

   R ^b is a hydrogen atom, optionally substituted C _1-12 alkyl, optionally substituted C _1-12 heteroalkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _5-24 aryl , Optionally substituted C _5-24 heteroaryl, optionally substituted C _5-24 cycloalkyl, optionally substituted C _5-24 heterocyclyl or optionally substituted benzyl;

   R ^1b is an optionally substituted C _5-24 aryl group, an optionally substituted C _5-24 heteroaryl group, an optionally substituted C _5-24 cycloalkyl group or an optionally substituted C _5-24 heterocyclic group.
6. The compound of claim 5, wherein:

   R ^b is a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 cycloalkyl, C _5-12 heterocycloalkyl, benzyl or C _{1 -6} alkyl substituted benzyl;

   R ^1b is C _1-6 alkyl substituted with C _5-12 aryl group, C _1-6 alkoxy substituted C _5-12 aryl, C _1-6 heteroaryl C _5-12 alkyl substituted aryl group, _{A C 5-12} aryl group, a C _5-12 cycloalkyl group or a C _5-12 heterocyclic group substituted by a C _{1-6 haloalkyl group.}
7. The compound of claim 5, wherein:

   R ^b is a hydrogen atom, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl Benzyl, benzyl, p-methylbenzyl, o-methylbenzyl or m-methylbenzyl;

   R ^1b is methyl, phenyl, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, 2,4-dimethoxyphenyl, 2,4,6-trimethoxy Phenyl, p-methylphenyl, p-fluorophenyl, p-trifluoromethylphenyl.
8. The compound of claim 5, which has one of the following structures:

   

   
9. A compound characterized in that the compound is a compound represented by formula (III), a compound represented by formula (VI), a stereoisomer of a compound represented by formula (III), or a stereoisomer of a compound represented by formula (VI) isomer,

   

   in,

   R ^c is a hydrogen atom, optionally substituted C _1-12 alkyl, optionally substituted C _1-12 heteroalkyl, optionally substituted C _2-12 alkenyl, optionally substituted C _5-24 cycloalkane Group, optionally substituted C _5-24 heterocyclyl or optionally substituted benzyl.
10. The compound of claim 1, wherein:

    R ^c is a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 cycloalkyl, C _5-12 heterocycloalkyl, benzyl, or C _1-6 alkyl substituted benzyl.
11. The compound of claim 1, wherein:

    R ^c is a hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl , Benzyl, p-methylbenzyl, o-methylbenzyl or m-methylbenzyl.
12. The compound according to claim 1, characterized in that it has one of the following structures:

    
13. A compound characterized in that the compound is a compound represented by formula (IV), a compound represented by formula (V), a compound represented by formula (VII), a stereoisomer of a compound represented by formula (IV), (V) the stereoisomer of the compound or the stereoisomer of the compound represented by formula (VII),

    

    in,

    R ^d , R ^1d , R ^2d and R ^3d are each independently a hydrogen atom, an optionally substituted C _1-12 alkyl group, an optionally substituted C _1-12 heteroalkyl group, and an optionally substituted C _2-12 alkene Group, optionally substituted C _5-24 aryl, optionally substituted C _5-24 heteroaryl, optionally substituted C _5-24 cycloalkyl, optionally substituted C _5-24 heterocyclyl or any Optional substituted benzyl.
14. The compound of claim 13, wherein:

    R ^d , R ^1d , R ^2d , and R ^3d are each independently a hydrogen atom, C _1-10 alkyl, C _1-10 heteroalkyl, C _2-6 alkenyl, C _5-12 aryl, C _{1- 6} Alkyl-substituted C _5-12 aryl, C _1-6 alkoxy-substituted C _5-12 aryl, cyano-substituted C _5-12 aryl, halogen-substituted C _5-12 aryl, C _5-12 cycloalkyl, C _5-12 heterocycloalkyl, benzyl or C _1-6 alkyl substituted benzyl.
15. The compound of claim 13, wherein:

    R ^d is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl;

    R ^1d , R ^2d , and R ^3d are each independently phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 4-cyanophenyl , 4-chlorophenyl, 4-fluorophenyl, 4-tert-butylphenyl, 4-isopropylphenyl, 1-naphthyl, 2-naphthyl, benzyl.
16. The compound according to claim 13, characterized in that it has one of the following structures:

    

    

    

    

    
17. A method for preparing the compound according to any one of claims 1 to 4, characterized in that it comprises: causing the compound represented by formula (VIII) to generate intramolecular Csp ² -N bonds in the presence of the first transition metal catalyst Coupling reaction to obtain the compound represented by formula (I),

    

    Wherein, R ^a is as claimed in any one of claims 1 to 4 as defined.
18. The method according to claim 17, wherein the first transition metal catalyst comprises selected from the group consisting of palladium chloride, palladium acetate, tris(dibenzylideneacetone)dipalladium, tris(dibenzylideneacetone)dipalladium chloroform At least one of the complex, tetrakistriphenylphosphine palladium, and ferrocene bisdiphenylphosphine palladium chloride.
19. The method according to claim 18, wherein the intramolecular Csp ² -N bond coupling reaction is carried out under the action of a phosphine ligand and a base, and the phosphine ligand comprises a group selected from the group consisting of triphenylphosphine, triphenylphosphine and triphenylphosphine. Tert-butyl phosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 1,3-bisdiphenylphosphine propane, ferrocene bisdiphenylphosphine, 4,5-bisdiphenylphosphine- At least one of 9,9-dimethylxanthene, 4'-dimethylaminophenyl bis-tert-butyl phosphine, and the base is selected from the group consisting of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide , At least one of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, potassium phosphate, triethylamine, and diisopropylethylamine.
20. The method according to claim 17, wherein the intramolecular Csp ² -N bond coupling reaction is carried out in a first solvent, and the first solvent comprises a solvent selected from the group consisting of chloroform, carbon tetrachloride, 1 ,2-Dichloroethane, 1,1,2,2-tetrachloroethane, benzene, toluene, trifluorotoluene, fluorobenzene, nitrobenzene, o-xylene, m-xylene, p-xylene, mixed two At least one of toluene, trimethylbenzene, and tetralin.
21. The method according to claim 20, wherein the intramolecular Csp ² -N bond coupling reaction is completed at 25-200° C. for 0.1-96 h.
22. The method according to claim 21, wherein the ratio of the compound represented by the formula (VIII) to the amount of the first transition metal catalyst is 0.01-1 mmol:0.01-100 mmol.
23. The method according to claim 21, characterized in that the amount ratio of the compound represented by the formula (VIII) to the phosphine ligand is 0.01-1 mmol:0.001-10 mmol.
24. The method according to claim 21, wherein the amount ratio of the compound represented by the formula (VIII) to the base is 0.01-1 mmol: 0.001-10 mmol.
25. A method for preparing the compound according to any one of claims 5 to 8, characterized in that it comprises: reacting the compound represented by formula (I-1) with R ^1b -X ⁰ to obtain the compound represented by formula (II) Compound.

    Alternatively, the compound represented by formula (IX) can undergo an intermolecular Csp ^{2 -N bond coupling reaction with R 1b} -NH ₂ in the presence of the first transition metal catalyst to obtain the compound represented by formula (II),

    

    Wherein, R ^b and R ^1b are defined in any one of claims 5 to 8, and X ⁰ is Cl, Br or I.
26. The method according to claim 25, wherein the first transition metal catalyst is selected from the group consisting of palladium chloride, palladium acetate, tris(dibenzylideneacetone)dipalladium, tris(dibenzylideneacetone)dipalladium chloroform At least one of the complex, tetrakistriphenylphosphine palladium, and ferrocene bisdiphenylphosphine palladium chloride.
27. The method according to claim 26, wherein the intermolecular Csp ² -N bond coupling reaction is carried out under the action of a phosphine ligand and a base, and the phosphine ligand comprises a group selected from the group consisting of triphenylphosphine, triphenylphosphine and triphenylphosphine. Tert-butyl phosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 1,3-bisdiphenylphosphine propane, ferrocene bisdiphenylphosphine, 4,5-bisdiphenylphosphine- At least one of 9,9-dimethylxanthene and 4'-dimethylaminophenyl bis-tert-butylphosphine. The base includes selected from lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, potassium phosphate, triethylamine, diisopropylethylamine At least one of them.
28. The method according to claim 25, wherein the intermolecular Csp ² -N bond coupling reaction is carried out in a second solvent, and the second solvent comprises a solvent selected from the group consisting of chloroform, carbon tetrachloride, 1 ,2-Dichloroethane, 1,1,2,2-tetrachloroethane, benzene, toluene, trifluorotoluene, fluorobenzene, nitrobenzene, o-xylene, m-xylene, p-xylene, mixed two At least one of toluene, trimethylbenzene, and tetralin.
29. The method of claim 28, wherein the intermolecular Csp ² -N bond coupling reaction is completed at 25 to 200° C. for 0.1 to 96 hours.
30. The method according to claim 28, wherein the amount ratio of the compound represented by the formula (I-1) to the first transition metal catalyst is 0.01-1 mmol:0.01-100 mmol.
31. The method according to claim 28, characterized in that the amount ratio of the compound represented by formula (I-1) to the phosphine ligand is 0.01-1 mmol:0.001-10 mmol.
32. The method according to claim 28, wherein the amount ratio of the compound represented by the formula (I-1) to the base is 0.01-1 mmol:0.001-10 mmol.
33. The method according to claim 28, wherein the amount ratio of the compound represented by the formula (IX) to the first transition metal catalyst is 0.01-1 mmol:0.01-100 mmol.
34. The method according to claim 28, characterized in that the amount ratio of the compound represented by formula (IX) to the phosphine ligand is 0.01-1 mmol:0.001-10 mmol.
35. The method according to claim 28, wherein the amount ratio of the compound represented by formula (IX) to the base is 0.01-1 mmol: 0.001-10 mmol.
36. A method for preparing the compound according to any one of claims 9-12, characterized in that it comprises:

    (1) Preparation of compound represented by formula (X) and compound represented by formula (XII)

    Make the compound of formula (IX) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a second transition metal catalyst, or make the compound of formula (IX) undergo a hydrolysis reaction and intramolecular aromatic nucleophilic substitution After reaction, the compound represented by formula (X) is obtained.

    Make the compound of formula (XI) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a second transition metal catalyst, or make the compound of formula (XI) undergo a hydrolysis reaction and intramolecular aromatic nucleophilic substitution Through the reaction, the compound represented by formula (XII) is obtained.

    (2) Preparation of compound represented by formula (III) and compound represented by formula (VI)

    Make the compound represented by formula (X) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a transition metal catalyst, or make the compound represented by formula (X) undergo a hydrolysis reaction and an intramolecular aromatic nucleophilic substitution reaction, The compound represented by formula (III) is obtained.

    Make the compound of formula (XII) undergo an intramolecular Csp ² -O bond coupling reaction in the presence of a second transition metal catalyst, or make the compound of formula (XII) undergo a hydrolysis reaction and intramolecular aromatic nucleophilic substitution Through the reaction, the compound represented by formula (VI) is obtained.

    

    

    Wherein, R ^c is defined in any one of claims 9-12.
37. The method according to claim 36, wherein the second transition metal catalyst comprises palladium acetate, palladium chloride, tetrakis(triphenylphosphine) palladium, [1,1'-bis(diphenylphosphine) Ferrocene] palladium dichloride, [1,1'-bis(diphenylphosphine) ferrocene] dichloride palladium dichloromethane complex, bis(triphenylphosphine) palladium dichloride, tris(diethylene) Benzylacetone) two palladium (0), tris (dibenzylidene acetone) two palladium (0) chloroform complex, bis (dibenzylidene acetone) palladium (0), allyl palladium chloride (II) two Polymer, bis(benzonitrile) palladium dichloride, bis(acetonitrile) palladium dichloride, 1,4-bis(diphenylphosphine)butane-palladium(II) chloride, bis(methyldiphenylphosphine) ) Palladium(II) dichloride, 1,1'-bis(di-tert-butylphosphine)ferrocene palladium dichloride, bis(tri-o-tolylphosphine)palladium(II) dichloride, bis(tricyclohexyl) Phosphine) at least one of palladium dichloride, [1,3-bis(diphenylphosphine)propane]palladium(II) chloride, and bis(tri-tert-butylphosphine)palladium.
38. The method according to claim 37, wherein the intramolecular Csp ² -O bond coupling reaction is carried out under the action of a phosphine ligand and a base, and the phosphine ligand comprises selected from triphenylphosphine, 2 -Biscyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphine-2',6'-Diisopropoxy-1,1'-biphenyl, 4,5-bisdiphenylphosphine-9,9-dimethylxanthene, 1,1'-bis(diphenylphosphine) dicene At least one of iron, 1,1'-binaphthol, 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl, tricyclohexylphosphine, and tri-tert-butylphosphine . The base includes selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, potassium phosphate, sodium phosphate, sodium tert-butoxide, potassium tert-butoxide, dipotassium hydrogen phosphate, triethylamine, N,N-dimethylamine At least one of pyridine and DBU.
39. The method according to claim 38, wherein the base used in the hydrolysis reaction comprises a base selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, potassium phosphate, sodium phosphate, sodium tert-butoxide, tert-butanol At least one of potassium, dipotassium hydrogen phosphate, triethylamine, N,N-dimethylaminopyridine, and DBU.
40. The method of claim 36, wherein the intramolecular Csp ² -O bond coupling reaction, the hydrolysis reaction, and the intramolecular aromatic nucleophilic substitution reaction are carried out in a third solvent, and the first The three solvents include selected from acetonitrile, tetrahydrofuran, xylene, 1,4-dioxane, tetralin, dimethyl sulfoxide, chlorobenzene, o-dichlorobenzene, benzyl acetonitrile, nitrobenzene, N,N- At least one of dimethylformamide, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoric triamide, and N-methylpyrrolidone.
41. The method of claim 40, wherein the intramolecular Csp ² -O bond coupling reaction is completed at 0-150°C for 0.1-96 h.
42. The method of claim 40, wherein the hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction are completed at 0-150°C for 0.1-96 hours.
43. The method according to claim 40, wherein the amount ratio of the compound represented by the formula (IX) to the second transition metal catalyst is 0.1 to 1 mmol: 0.01 to 0.1 mmol.
44. The method according to claim 40, wherein the amount ratio of the compound represented by the formula (XI) to the second transition metal catalyst is 0.1-1 mmol:0.01-0.1 mmol.
45. The method according to claim 40, characterized in that the amount ratio of the compound represented by formula (IX) to the phosphine ligand is 0.01-1mmol:0.001-10mmol,
46. The method according to claim 40, wherein the amount ratio of the compound represented by the formula (XI) to the phosphine ligand is 0.01-1 mmol:0.001-10 mmol.
47. The method according to claim 40, characterized in that the amount ratio of the compound represented by formula (IX) to the base is 0.01-1 mmol:0.001-10 mmol.
48. The method according to claim 40, characterized in that the ratio of the amount of the compound represented by formula (XI) to the base used in the hydrolysis reaction is 0.01-1 mmol:0.001-10 mmol.
49. The method according to claim 40, wherein the ratio of the amount of the compound represented by formula (IX) to the base used in the hydrolysis reaction is 0.01-1 mmol:0.001-10 mmol.
50. A method for preparing the compound according to any one of claims 9-12, characterized in that it comprises:

    The compound represented by formula (IX) or the compound represented by formula (XIII) is subjected to selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction in sequence under the action of a base to obtain the compound represented by formula (III).

    The compound represented by formula (XI) or the compound represented by formula (XIV) is subjected to selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction in sequence under the action of a base to obtain the compound represented by formula (VI).

    

    Wherein, R ^c is defined in any one of claims 9-12.
51. The method according to claim 50, wherein the base comprises a base selected from the group consisting of potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, potassium phosphate, sodium phosphate, sodium tert-butoxide, potassium tert-butoxide, dibasic hydrogen phosphate At least one of potassium, triethylamine, N,N-dimethylaminopyridine, and DBU.
52. The method according to claim 51, wherein the selective hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction are carried out in a fourth solvent, and the fourth solvent comprises a solvent selected from the group consisting of acetonitrile, tetrahydrofuran, 1 ,4-Dioxane, N,N-dimethylformamide, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone, phenylacetonitrile , At least one of nitrobenzene.
53. The method according to claim 52, wherein the selective hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction are completed at 0-150°C for 0.1-96 hours.
54. The method according to claim 52, wherein the amount ratio of the compound represented by formula (IX) to the base is 0.01-1 mmol: 0.001-10 mmol.
55. The method according to claim 52, wherein the amount ratio of the compound represented by the formula (XI) to the base is 0.01-1 mmol: 0.001-10 mmol.
56. The method according to claim 52, wherein the amount ratio of the compound represented by the formula (XIII) to the base is 0.01-1 mmol:0.001-20 mmol.
57. The method according to claim 52, wherein the amount ratio of the compound represented by the formula (XIV) to the base is 0.01-1 mmol: 0.001-20 mmol.
58. A method for preparing the compound according to any one of claims 13-16, characterized in that it comprises:

    (1) Preparation of compound represented by formula (XV)

    The compound represented by the formula (X-1) is subjected to the first intermolecular Csp ² -heterobond coupling reaction and the first intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by the formula (XV). The first intermolecular Csp ² -heterobond coupling reaction and the first intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst and R ^1d -NH ₂ .

    (2) Preparation of compound represented by formula (IV)

    The compound represented by formula (X-1) is subjected to the second intermolecular Csp ² -heterobond coupling reaction and the second intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by formula (IV). ^{The Csp 2} -heterobond coupling reaction between two molecules and the second intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst, R ^1d -NH ₂ , and R ^2d -NH ₂ .

    Alternatively, the compound represented by the formula (XV) is subjected to the third intermolecular Csp ² -heterobond coupling reaction and the third intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by the formula (IV). The third intermolecular Csp ² -heterobond coupling reaction and the third intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst and R ^2d -NH ₂ .

    (3) Preparation of compound represented by formula (VII)

    The compound represented by the formula (XII-1) is subjected to a fourth intermolecular Csp ² -heterobond coupling reaction and a fourth intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by the formula (VII). The fourth intermolecular Csp ² -heterobond coupling reaction and the fourth intramolecular Csp ² -heterobond coupling reaction are in the second transition metal catalyst and R ^1d -NH ₂ , R ^2d -NH ₂ , R ^3d It is carried out in the presence of _{-NH 2.}

    (4) Preparation of compound represented by formula (V)

    The compound represented by formula (X-1) is subjected to the fifth intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by formula (V). The five intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst and R ^1d -NH ₂ .

    Alternatively, the compound represented by formula (XV) is subjected to a sixth intermolecular Csp ² -heterobond coupling reaction and a sixth intramolecular Csp ² -heterobond coupling reaction in sequence to obtain the compound represented by formula (V). The sixth intermolecular Csp ² -heterobond coupling reaction and the sixth intramolecular Csp ² -heterobond coupling reaction are carried out in the presence of a second transition metal catalyst.

    Alternatively, the compound represented by formula (XV) is subjected to selective hydrolysis reaction and intramolecular aromatic nucleophilic substitution reaction in sequence under the action of a base to obtain the compound represented by formula (V).

    

    Among them, R ^d , R ^1d , R ^2d , and R ^3d are defined in any one of claims 13-16.
59. The method according to claim 58, wherein the second transition metal catalyst comprises selected from the group consisting of palladium acetate, palladium chloride, tetrakis(triphenylphosphine) palladium, [1,1'-bis(diphenyl) Phosphine)ferrocene]palladium dichloride, [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium dichloromethane complex, bis(triphenylphosphine)palladium dichloride, tris( Dibenzylideneacetone)dipalladium(0), tris(dibenzylideneacetone)dipalladium(0) chloroform complex, bis(dibenzylideneacetone)palladium(0), allylpalladium(II) chloride ) Dimer, bis(benzonitrile) palladium dichloride, bis(acetonitrile) palladium dichloride, 1,4-bis(diphenylphosphine)butane-palladium(II) chloride, bis(methyl dichloride) Phenylphosphine) palladium(II) dichloride, 1,1'-bis(di-tert-butylphosphine)ferrocene palladium dichloride, bis(tri-o-toluenephosphine)palladium(II), bis(tri At least one of cyclohexylphosphine)palladium dichloride, [1,3-bis(diphenylphosphine)propane]palladium(II) chloride, and bis(tri-tert-butylphosphine)palladium.
60. The method of claim 59, wherein the first intermolecular Csp ² -heterobond coupling reaction, the first intramolecular Csp ² -heterobond coupling reaction, and the second intermolecular Csp ^{2 -heterobond} Coupling reaction, second intramolecular Csp ² -heterobond coupling reaction, third intermolecular Csp ² -heterobond coupling reaction, third intramolecular Csp ² -heterobond coupling reaction, fourth intermolecular Csp ^2- Heterobond coupling reaction, the fourth intramolecular Csp ² -heterobond coupling reaction, the fifth intermolecular Csp ² -heterobond coupling reaction, the fifth intramolecular Csp ² -heterobond coupling reaction, the sixth intermolecular Csp ^{The 2} -hetero-bond coupling reaction and the sixth intramolecular Csp ² -hetero-bond coupling reaction are carried out under the action of a phosphine ligand and a base, and the phosphine ligand includes a group selected from triphenylphosphine and 2-bicyclohexylphosphine- 2',4',6'-Triisopropylbiphenyl, 2-Biscyclohexylphosphine-2',6'-Dimethoxybiphenyl, 2-Biscyclohexylphosphine-2',6'-Diisopropyloxy 1,1'-biphenyl, 4,5-bisdiphenylphosphine-9,9-dimethylxanthene, 1,1'-bis(diphenylphosphine)ferrocene, 1,1 At least one of'-binaphthol, 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl, tricyclohexylphosphine, and tri-tert-butylphosphine. The base includes selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, sodium acetate, potassium acetate, lithium acetate, potassium phosphate, sodium phosphate, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, tert-butoxide At least one of potassium alkoxide, tetrabutylammonium hydroxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, triethylamine, diethylamine, N,N-diisopropylethylamine, and DBU.
61. The method of claim 59, wherein the first intermolecular Csp ² -heterobond coupling reaction, the first intramolecular Csp ² -heterobond coupling reaction, and the second intermolecular Csp ^{2 -heterobond} Coupling reaction, second intramolecular Csp ² -heterobond coupling reaction, third intermolecular Csp ² -heterobond coupling reaction, third intramolecular Csp ² -heterobond coupling reaction, fourth intermolecular Csp ^2- Heterobond coupling reaction, the fourth intramolecular Csp ² -heterobond coupling reaction, the fifth intermolecular Csp ² -heterobond coupling reaction, the fifth intramolecular Csp ² -heterobond coupling reaction, the sixth intermolecular Csp ^{The 2} -hetero-bond coupling reaction and the sixth intramolecular Csp ² -hetero-bond coupling reaction are carried out in a fifth solvent, and the fifth solvent is selected from xylene, 1,1,2,2-tetrachloroethane , Benzene, toluene, benzotrifluoride, chlorobenzene, fluorobenzene, nitrobenzene, bromobenzene, o-xylene, m-xylene, p-xylene, N,N-dimethylformamide and tetralin at least one.
62. The method of claim 59, wherein the first intermolecular Csp ² -heterobond coupling reaction, the first intramolecular Csp ² -heterobond coupling reaction, and the second intermolecular Csp ^{2 -heterobond} Coupling reaction, second intramolecular Csp ² -heterobond coupling reaction, third intermolecular Csp ² -heterobond coupling reaction, third intramolecular Csp ² -heterobond coupling reaction, fourth intermolecular Csp ^2- Heterobond coupling reaction, the fourth intramolecular Csp ² -heterobond coupling reaction, the fifth intermolecular Csp ² -heterobond coupling reaction, the fifth intramolecular Csp ² -heterobond coupling reaction, the sixth intermolecular Csp ^{The 2} -hetero-bond coupling reaction and the Csp ² -hetero-bond coupling reaction in the sixth molecule are completed at 0-200°C for 0.1-96 hours.
63. The method of claim 59, wherein in the first intermolecular Csp ² -heterobond coupling reaction and the first intramolecular Csp ² -heterobond coupling reaction, the formula (X-1) ^{The dosage} ratio of the compound shown to R 1d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol.
64. The method according to claim 59, wherein in the second intermolecular Csp ² -heterobond coupling reaction and the second intramolecular Csp ² -heterobond coupling reaction, the formula (X-1) ^{The dosage} ratio of the compound to R 1d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol, and the dosage ratio of the compound represented by formula (X-1) to R ^2d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol.
65. The method of claim 59, wherein the third intermolecular Csp ² -heterobond coupling reaction and the third intramolecular Csp ² -heterobond coupling reaction are represented by formula (XV) The dosage ratio of the compound to R ^2d _{-NH 2} is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (XV) to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (XV) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by formula (XV) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol.
66. The method of claim 59, wherein the fourth intermolecular Csp ² -heterobond coupling reaction and the fourth intramolecular Csp ² -heterobond coupling reaction are of formula (XII-1) ^{The dosage} ratio of the compound shown to R 1d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol, and the ^dosage ratio of the compound shown in formula (XII-1) to R 2d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol, the formula ( The dosage ratio of the compound shown in XII-1) to R ^3d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (XII-1) to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by formula (XII-1) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (XII-1) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol.
67. The method according to claim 59, wherein in the fifth intermolecular Csp ² -heterobond coupling reaction and the fifth intramolecular Csp ² -heterobond coupling reaction, formula (X-1) The dosage ratio of the compound to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (X-1) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol. ^{The dosage} ratio of the compound represented by formula (X-1) to R 1d -NH ₂ is 0.0001 to 1 mol: 0.0001 to 10 mol.
68. The method of claim 59, wherein the sixth intermolecular Csp ² -heterobond coupling reaction and the sixth intramolecular Csp ² -heterobond coupling reaction are represented by formula (XV) The dosage ratio of the compound to the second transition metal catalyst is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by the formula (XV) to the phosphine ligand is 0.0001 to 1 mol: 0.0001 to 10 mol. The dosage ratio of the compound represented by formula (XV) to the base is 0.0001 to 1 mol: 0.0001 to 20 mol.
69. The method according to claim 59, wherein the selective hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction and the base comprise selected from potassium carbonate, cesium carbonate, lithium carbonate, sodium carbonate, potassium phosphate, At least one of sodium phosphate, sodium tert-butoxide, potassium tert-butoxide, dipotassium hydrogen phosphate, triethylamine, N,N-dimethylaminopyridine, and DBU.
70. The method according to claim 59, wherein the selective hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction are carried out in a sixth solvent, and the sixth solvent comprises a solvent selected from the group consisting of acetonitrile, tetrahydrofuran, 1, 4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone, benzyl acetonitrile, At least one of nitrobenzene.
71. The method of claim 59, wherein the selective hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction are completed at 0-200°C for 0.1-96 hours.
72. The method according to claim 59, wherein in the selective hydrolysis reaction and the intramolecular aromatic nucleophilic substitution reaction, the amount ratio of the compound represented by formula (XV) to the base is 0.0001 to 1 mol: 0.0001～10mol.

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