阅读说明：本技术 2-芳基苯并氮杂卓及其衍生物的合成方法 (Synthesis method of 2-aryl benzazepine and derivatives thereof ) 是由 张兴国 曾猛强 张小红 涂海勇 于 2021-09-01 设计创作，主要内容包括：本发明涉及一种2-芳基苯并氮杂卓及其衍生物的合成方法,包括以下步骤：以2-卤代苯胺和芳基环丁醇为反应底物,以氯化钯为催化剂,三环己基膦为配体,碳酸铯作碱,超干甲苯作溶剂,于110 ～(o)C在氮气氛围中搅拌反应12小时。该方法具有原料简单易得、反应条件相对温和、底物普适性广,制备工艺新颖、耗能低等优点。(The invention relates to a synthetic method of 2-aryl benzazepine and derivatives thereof, which comprises the following steps: taking 2-halogenated aniline and aryl cyclobutanol as reaction substrates, palladium chloride as a catalyst, tricyclohexylphosphine as a ligand, cesium carbonate as alkali and ultra-dry toluene as a solvent, and reacting at 110 o C the reaction was stirred under nitrogen atmosphere for 12 hours. The method has the advantages of simple and easily obtained raw materials, relatively mild reaction conditions, wide substrate universality, novel preparation process, low energy consumption and the like.)

1. A method for synthesizing 2-aryl benzazepine and derivatives thereof comprises the following steps: taking 2-halogenated aniline and aryl cyclobutanol as reaction substrates, palladium acetate, palladium chloride and palladium trifluoroacetate as catalysts, tricyclohexylphosphine as a ligand, potassium phosphate, cesium carbonate and potassium tert-butoxide as bases, and ultra-dry N, N-dimethylformamide, ultra-dry tetrahydrofuran, ultra-dry 1, 2-dichloroethane and ultra-dry toluene as solvents, and dissolving the solvents in a solvent of 100-120%^oC is stirred and reacted for 12 hours in a nitrogen atmosphere, and the chemical reaction formula is as follows:

the-X is: chlorine atom, bromine atom, iodine atom;

and-Ar is: one of phenyl, 4-methylphenyl, 5-methylphenyl, 4-methoxyphenyl, 5-trifluoromethylphenyl, 5-carbomethoxyphenyl, 5-fluorophenyl, 4-chlorophenyl, 5-chlorophenyl and 1-naphthyl;

the-R is one of a hydrogen atom, phenyl and benzyloxy;

-R' is: phenyl, 2-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 4-tert-butylphenylA group, 4-methoxyphenyl group, 3, 4-benzo [ b ], [ 2 ]d][1,3]Dioxolane, 4-fluorophenyl group, 4-chlorophenyl group, 3-trifluoromethylphenyl group, 2-naphthyl group, 4- [1, 1']One of-biphenyl and 2-thiophene, wherein 3, 4-benzo [ b ], [ 2 ]d][1,3]The dioxolane has the structural formula；4-[1,1’]-biphenyl of the formula(ii) a The structural formula of the 2-thiophene is。

2. A process for the synthesis of 2-arylbenzazepines and derivatives thereof according to claim 1 wherein: the catalyst is palladium chloride.

3. A process for the synthesis of 2-arylbenzazepines and derivatives thereof according to claim 1 wherein: the ligand is tricyclohexylphosphine.

4. A process for the synthesis of 2-arylbenzazepines and derivatives thereof according to claim 1 wherein: the base is cesium carbonate.

5. A process for the synthesis of 2-arylbenzazepines and derivatives thereof according to claim 1 wherein: the solvent is ultra-dry toluene.

6. A process for the synthesis of 2-arylbenzazepines and derivatives thereof according to claim 1 wherein: the reaction temperature was 110 ℃.

7. A process for the synthesis of 2-arylbenzazepines and derivatives thereof according to claim 1 wherein: and filtering after the reaction is finished, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, carrying out rotary evaporation on the combined organic layers by using a rotary evaporator to remove the solvent to obtain a residue, carrying out column layer separation on the residue through a silica gel column, carrying out elution by using an eluent, collecting an effluent containing the target product, combining the effluent, and removing the solvent by vacuum concentration to obtain the target product.

Technical Field

The invention relates to a preparation method of 2-aryl benzazepine and derivatives thereof.

Background

Nitrogen-containing seven-membered heterocycles are important structural motifs in pharmaceutical and material chemistry and can be found in a variety of biologically active molecules, natural products, dipeptides and dyes. 1-Benzazepine derivatives are a typical representative, due to their antidepressants (A)Beilstein J. Org. Chem.2015, 11, 1509-Bioorg. Med. Chem.2010, 18, 4721-J. Med. Chem. 2000, 43, 4388-J. Med. Chem. 1998, 41, 1299-1305.), etc., have attracted considerable attention. However, the traditional method for constructing 1-benzazepine drugs always has multi-step ring closure reaction under harsh conditions. In recent years, ring expansion reactions have been developed as powerful tools for the synthesis of benzazepine derivatives (medium-sized nitrogen-containing heterocycles). For example, indole, 4-pyrrolidinyl, azapyridine, quinoline derivatives, and the like may be converted to a variety of 1-benzazepine drugs under certain conditions.

However, the above methods have disadvantages of multistep reaction, low economy, low yield, and the like, and therefore, it is highly desirable to find general and simple methods for constructing a benzazepine skeleton from easily available raw materials. Based on the reaction, the invention provides a novel method for synthesizing 2-aryl benzazepine and derivatives thereof, which has the advantages of wide substrate application range, easily obtained raw materials, high efficiency, simple operation, safety and no pollution.

Disclosure of Invention

Aiming at the defects existing at the present stage, the invention provides a method for synthesizing 2-aryl benzazepine and derivatives thereof, which uses 2-halogenated aniline and aryl cyclobutanol as reaction substrates, and has the advantages of simple technical process, high yield and relatively mild reaction conditions.

In order to achieve the purpose, the invention adopts the technical scheme that:

a method for synthesizing 2-aryl benzazepine and derivatives thereof comprises the following steps: taking 2-halogenated aniline and aryl cyclobutanol as reaction substrates, palladium acetate, palladium chloride and palladium trifluoroacetate as catalysts, tricyclohexylphosphine as a ligand, potassium phosphate, cesium carbonate and potassium tert-butoxide as bases, and ultra-dry N, N-dimethylformamide, ultra-dry tetrahydrofuran, ultra-dry 1, 2-dichloroethane and ultra-dry toluene as solvents, and dissolving the solvents in a solvent of 100-120%^oC is stirred and reacted for 12 hours in a nitrogen atmosphere, and the chemical reaction formula is as follows:

the-X is: chlorine atom, bromine atom, iodine atom;

and-Ar is: one of phenyl, 4-methylphenyl, 5-methylphenyl, 4-methoxyphenyl, 5-trifluoromethylphenyl, 5-carbomethoxyphenyl, 5-fluorophenyl, 4-chlorophenyl, 5-chlorophenyl and 1-naphthyl;

the-R is one of a hydrogen atom, phenyl and benzyloxy;

-R' is: phenyl group, 2-methylphenyl group, 4-methylphenyl group, 3, 5-dimethylphenyl group, 4-tert-butylphenyl group, 4-methoxyphenyl group, 3, 4-benzo [ b ], [ 2 ] phenyl groupd][1,3]Dioxolane, 4-fluorophenyl group, 4-chlorophenyl group, 3-trifluoromethylphenyl group, 2-naphthyl group, 4- [1, 1']One of-biphenyl and 2-thiophene, wherein 3, 4-benzo [ b ], [ 2 ]d][1,3]The dioxolane has the structural formula；4-[1,1’]-biphenyl of the formula(ii) a The structural formula of the 2-thiophene is。

The preparation method adopted by the invention is characterized in that 2-aryl benzazepine and derivatives thereof are synthesized by reacting 2-halogenated aniline and aryl cyclobutanol under the action of palladium chloride as a catalyst, tricyclohexylphosphine as a ligand, cesium carbonate as an alkali and ultra-dry toluene as a solvent, the process is simple, special instruments or modes are not required, the preparation method is very suitable for operation of people in the field, and the preparation method has the advantages of simple operation, easy obtaining of products and the like.

In a further embodiment of the invention, the catalyst is palladium chloride.

In a further embodiment of the invention, the base is cesium carbonate.

In a further embodiment of the present invention, the solvent is ultra-dry toluene.

In a further development of the invention, the reaction temperature is 110 ℃.

The method can directly synthesize the target product without separating intermediate products, can obtain the target product by a simple separation method, has the highest yield of 90 percent, greatly simplifies process engineering, reduces energy consumption and has excellent yield; and in the reaction process, the waste solution is less, and other polluted gases and liquid are not discharged, so that the method reduces the discharge of the waste solution, and has the advantages of protecting the environment and ensuring the health of operators. In addition, a series of 2-aryl benzazepines and derivatives thereof can be prepared, and the method has better substrate universality.

The mechanism of the invention is as follows: firstly, the oxidative addition of 2-bromoaniline and Pd (0) obtains aryl Pd (II) intermediate A, then ligand exchange is carried out, and the aryl Pd (II) intermediate A is combined with cyclobutanol anions to generate palladium alkoxide B. Subsequently, a ring opening process occurs by β -carbon elimination to give the alkyl palladium intermediate C. Pd (II) intermediate C is readily reductively eliminated to yield gamma-arylated ketone D and Pd (0) species. Finally, the gamma-arylated ketone D is subjected to intramolecular dehydration condensation to obtain a target product. Possible reaction mechanisms the chemical reaction formula is as follows:

Detailed Description

The invention discloses a synthetic method of 2-aryl benzazepine and derivatives thereof, which comprises the following steps: taking 2-halogenated aniline and aryl cyclobutanol as reaction substrates, palladium acetate, palladium chloride and palladium trifluoroacetate as catalysts, tricyclohexylphosphine as a ligand, potassium phosphate, cesium carbonate and potassium tert-butoxide as bases, and ultra-dry N, N-dimethylformamide, ultra-dry tetrahydrofuran, ultra-dry 1, 2-dichloroethane and ultra-dry toluene as solvents, and dissolving the solvents in a solvent of 100-120%^oC is stirred and reacted for 12 hours in a nitrogen atmosphere, and the chemical reaction formula is as follows:

the-X is: chlorine atom, bromine atom, iodine atom;

and-Ar is: phenyl, 4-methylphenyl, 5-methylphenyl, 4-methoxyphenyl, 5-trifluoromethylphenyl, 5-carbomethoxyphenyl, 5-fluorophenyl, 4-chlorophenyl, 5-chlorophenyl, and 1-naphthyl.

the-R is one of a hydrogen atom, phenyl and benzyloxy;

-R' is: phenyl group, 2-methylphenyl group, 4-methylphenyl group, 3, 5-dimethylphenyl group, 4-tert-butylphenyl group, 4-methoxyphenyl group, 3, 4-benzo [ b ], [ 2 ] phenyl groupd][1,3]Dioxolane, 4-fluorophenyl group, 4-chlorophenyl group, 3-trifluoromethylphenyl group, 2-naphthyl group, 4- [1, 1']One of-biphenyl and 2-thiophene, wherein 3, 4-benzo [ b ], [ 2 ]d][1,3]The dioxolane has the structural formula；4-[1,1’]-biphenyl of the formula(ii) a The structural formula of the 2-thiophene is。

After the reaction, filtration was performed, the filtrate was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate, and the combined organic layers were subjected to rotary evaporation using a rotary evaporator to remove the solvent to obtain a residue. Eluting the residue with eluent prepared from ethyl acetate and petroleum ether at a volume ratio through a silica gel column, collecting the effluent according to actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent with a rotary evaporator, and finally drying in vacuum to obtain the target product.

The first embodiment is as follows: 2-chloroaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying the extract with anhydrous sodium sulfate, andand removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting the effluent according to the actual gradient, detecting by using TLC (thin layer chromatography), combining the effluent containing the target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain yellow oil drops of 18.5 mg of 2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 42%.¹H NMR (500 MHz, CDCl₃) δ 8.02-8.00 (m, 2H), 7.48-7.47 (m, 3H), 7.34-7.31 (m, 1H), 7.20-7.18 (m, 2H), 7.10-7.07 (m, 1H), 2.65 (t, J = 7.0 Hz, 2H), 2.56 (t, J = 7.5 Hz, 2H), 2.42-2.37 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 171.4, 149.9, 139.2, 131.3, 130.4, 128.8, 128.5, 127.2, 124.5, 123.8, 34.5, 30.3, 28.8。

The second embodiment is as follows: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 38.4 mg of yellow oil-dropped 2-phenyl-4, 5-dihydro-3H-benzazepine, wherein the yield is 87%.

The third concrete embodiment: mixing 2-iodoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, and extracting with ethyl acetateThen drying the mixture by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting the effluent according to the actual gradient, detecting by using TLC (thin layer chromatography), combining the effluent containing the target product, rotatably removing the solvent from the combined effluent by using the rotary evaporator, and drying in vacuum to obtain yellow oil drops of 37.5 mg of 2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 85%.

The fourth concrete embodiment: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), Pd (OAc)₂（2.2mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to a volume ratio of 1:60 through a silica gel column, collecting an effluent according to an actual gradient, detecting by TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by rotating with the rotary evaporator, and drying in vacuum to obtain 24.3 mg of yellow oil-drop 2-phenyl-4, 5-dihydro-3H-benzazepine with a yield of 55%.

The fifth concrete embodiment: 2-Bromophenylamine (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), Pd (TFA)₂（3.3mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with rotary evaporator to obtain residue, eluting the residue with silica gel column with eluent prepared from ethyl acetate and petroleum ether at a volume ratio of 1:60, collecting eluate according to actual gradient, detecting by TLC, mixing eluates containing target product, and rotating the mixed eluates with rotary evaporator to remove solventSolvent was removed and dried in vacuo to afford yellow oil droplets of 22.5 mg of 2-phenyl-4, 5-dihydro-3H-benzazepine in 51% yield.

The sixth specific embodiment: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、K₃PO₄(84.8 mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 29.6 mg of yellow oil-drop 2-phenyl-4, 5-dihydro-3H-benzazepine, wherein the yield is 67%.

The seventh specific embodiment: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、t-BuOK (44.8 mg), 4A MS (100.0mg) was added to ultra dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain yellow oil drops of 33.6 mg of 2-phenyl-4, 5-dihydro-3H-benzazepine, wherein the yield is 76%.

The eighth embodiment: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was addedTo ultra-dry tetrahydrofuran (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain yellow oil drops of 33.2 mg of 2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 75%.

The specific embodiment is nine: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry N, N-dimethylformamide (2 mL) at 110A^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 30.5 mg of yellow oil-drop 2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 69%.

The specific embodiment ten: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry 1, 2-dichloroethane (2 mL) at 110A^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with rotary evaporator to obtain residue, passing the residue through silica gel column, and eluting with ethyl acetateEluting with petroleum ether according to a volume ratio of 1:60, collecting effluent according to actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent by using a rotary evaporator, and drying in vacuum to obtain yellow oil drops of 33.2 mg of 2-phenyl-4, 5-dihydro-3H-benzazepine with a yield of 75%.

The first specific embodiment: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 120A^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 32.3 mg of yellow oil-drop 2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 73%.

The specific example twelve: 2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 100^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 23.9 mg of yellow oil-drop 2-phenyl-4, 5-dihydro-3H-benzazepine, wherein the yield is 54%.

The specific example thirteen: 4-methyl-2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 33.8 mg of yellow oil-drop 7-methyl-2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 72%.¹H NMR (500 MHz, CDCl₃) δ 7.98-7.96 (m, 2H), 7.43-7.42 (m, 3H), 7.11-7.06 (m, 2H), 6.98 (s, 1H), 2.61 (t, J = 7.5 Hz, 2H), 2.49 (t, J = 7.5 Hz, 2H), 2.37-2.31 (m, 5H). ¹³C NMR (125 MHz, CDCl₃) δ 171.0, 147.3, 139.3, 134.0, 131.2, 130.2, 129.4, 128.4, 127.7, 127.1, 123.8, 34.5, 30.3, 28.8, 20.9。

The specific embodiment fourteen: 5-methyl-2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to a volume ratio of 1:60 through a silica gel column, collecting the effluent according to actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain yellow oil drop 8-methyl-2-phenyl-4, 5-dihydro-3H-40.9 mg of benzazepine, 87% yield.¹H NMR (500 MHz, CDCl₃) δ 8.02-8.00 (m, 2H), 7.48-7.46 (m, 3H), 7.08 (d, J= 7.5 Hz, 1H), 7.03 (s, 1H), 6.90 (d, J = 7.5 Hz, 1H), 2.65 (t, J = 7.0 Hz, 2H), 2.52 (t, J = 7.0 Hz, 2H), 2.40-2.34 (m, 5H). ¹³C NMR (125 MHz, CDCl₃) δ 171.3, 149.7, 139.2, 136.8, 130.3, 128.6, 128.5, 128.3, 127.2, 125.3, 124.5, 34.5, 29.9, 28.9, 21.1。

The specific embodiment fifteen: 6-methyl-2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 24.9 mg of yellow oil drop 9-methyl-2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 53%.¹H NMR (500 MHz, CDCl₃) δ 7.96-7.94 (m, 2H), 7.37-7.35 (m, 3H), 7.05 (d, J= 7.0 Hz, 1H), 6.93-6.87 (m, 2H), 2.52 (t, J = 7.5 Hz, 2H), 2.41 (t, J = 7.5 Hz, 2H), 2.29-2.23 (m, 5H). ¹³C NMR (125 MHz, CDCl₃) δ 169.5, 148.0, 139.2, 131.7, 130.7, 130.2, 128.6, 128.5, 127.1, 126.2, 124.3, 34.4, 30.4, 28.8, 17.9。

The specific embodiment is sixteen: 4-methoxy-2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours.Filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain 24.6 mg of yellow oil drop 7-methoxy-2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 49%.¹H NMR (500 MHz, CDCl₃) δ 8.01-7.98 (m, 2H), 7.47-7.45 (m, 3H), 7.14 (d, J= 8.5 Hz, 1H), 6.87 (dd, J = 8.5, 3.0 Hz, 1H), 6.77(d, J = 3.0 Hz, 1H), 3.83 (s, 3H), 2.65 (t, J = 7.5 Hz, 2H), 2.53 (t, J = 7.5 Hz, 2H), 2.41-2.36 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 170.7, 156.5, 143.2, 139.4, 132.8, 130.1, 128.4, 127.0, 125.1, 114.4, 112.0, 55.3, 34.2, 30.8, 28.8。

Specific example seventeen: 5-trifluoromethyl-2-bromoaniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating way, and drying in vacuum to obtain 40.5 mg of yellow oil drop 2-phenyl-8-trifluoromethyl-4, 5-dihydro-3H-benzazepine with the yield of 70%.¹H NMR (500 MHz, CDCl₃) δ 8.02-8.00 (m, 2H), 7.52-7.46 (m, 3H), 7.44 (s, 1H), 7.33-7.28 (m, 2H), 2.66 (t, J = 7.5 Hz, 2H), 2.60 (t, J = 7.5 Hz, 2H), 2.45-2.39 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 172.7, 150.3, 138.6, 135.1, 130.9, 129.8 (² J = 32.1 Hz), 129.2, 128.6, 127.3, 124.3 (¹ J = 270.4 Hz), 121.1 (³ J = 3.6 Hz), 120.7 (³ J = 3.6 Hz), 34.3, 30.2, 28.7. ¹⁹F NMR (470 MHz, CDCl₃): δ -62.403(s, 3F)。

The specific embodiment eighteen: 3-amino-4-bromo-benzoic acid methyl ester (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating way, and drying in vacuum to obtain 44.1 mg of yellow oil-drop 2-phenyl-4, 5-dihydro-3H-benzazepine-8-methyl formate with the yield of 79%.¹H NMR (500 MHz, CDCl₃) δ 8.01-8.00 (m, 2H), 7.84 (s, 1H), 7.75 (dd, J = 7.5, 1.0 Hz,1H), 7.48-7.47 (m, 3H), 7.25 (d, J = 7.0 Hz, 1H), 3.92 (s, 3H), 2.65-2.58 (m, 4H), 2.44-2.38 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 172.1, 167.1, 150.0, 138.8, 136.6, 130.7, 129.4, 128.9, 128.6, 127.2, 125.7, 124.9, 52.0, 34.2, 30.4, 28.7。

The specific examples are nineteen: 5-fluoro-2-bromo-aniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, and adding saturated sodium chloride solutionWashing, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain yellow oil drops of 8-fluoro-2-phenyl-4, 5-dihydro-3H benzazepine 36.3 mg with the yield of 76%.¹H NMR (500 MHz, CDCl₃) δ 8.01-7.99 (m, 2H), 7.51-7.45 (m, 3H), 7.12 (dd, J = 8.0, 6.5 Hz, 1H), 6.90 (dd, J = 10.0, 2.5 Hz, 1H), 6.77 (td, J = 8.5, 2.5 Hz 1H), 2.65 (t, J = 7.5 Hz, 2H), 2.51 (t, J = 7.5 Hz, 2H), 2.40-2.34 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 172.4, 162.3 (¹ J = 241.9 Hz), 151.3 (³ J = 10.0 Hz), 138.8, 130.7, 129.6(³ J = 8.9 Hz), 128.6, 127.3, 127.0 (⁴ J = 3.0 Hz), 111.0 (² J= 21.1 Hz), 110.7 (² J = 22.5 Hz), 34.5, 29.6, 28.9. ¹⁹F NMR (470 MHz, Acetone-d ₆ ) δ -59.464 (s, 1F)。

The specific embodiment twenty: 4-chloro-2-bromo-aniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to a volume ratio of 1:60 through a silica gel column, collecting the effluent according to actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating with a rotary evaporator, and drying in vacuum to obtain yellow oil drop 7-chloro-2-phenyl-4, 5-dihydro-3H-benzazepine 39.8 mg, wherein the yield is 39.8 mg78%。¹H NMR (500 MHz, CDCl₃) δ 7.99-7.97 (m, 2H), 7.49-7.44 (m, 3H), 7.27-7.25 (m, 1H), 7.17 (d, J = 2.5 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H), 2.63 (t, J = 7.5 Hz, 2H), 2.51 (t, J = 7.5 Hz, 2H), 2.40-2.35 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 172.0, 148.4, 138.8, 133.1, 130.6, 129.4, 128.64, 128.59, 127.21, 127.18, 125.2, 34.2, 30.2, 28.8。

The specific embodiment twenty one: 5-chloro-2-bromo-aniline (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating manner, and drying in vacuum to obtain yellow oil drops, namely 39.8 mg of 8-chloro-2-phenyl-4, 5-dihydro-3H-benzazepine, wherein the yield is 78%.¹H NMR (500 MHz, CDCl₃) δ 8.00-7.98 (m, 2H), 7.49-7.46 (m, 3H), 7.18 (d, J = 2.0 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.04 (dd, J = 8.0, 2.0 Hz, 1H), 2.64 (t, J= 7.5 Hz, 2H), 2.52 (t, J = 7.5 Hz, 2H), 2.40-2.34 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 172.5, 151.1, 138.7, 132.7, 130.7, 129.8, 128.6, 127.3, 124.4, 123.8, 34.3, 29.8, 28.8。

The specific embodiment twenty two: 3-bromonaphthalene-2-amine (0.2 mmol), 1-phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC stirring and reacting for 12 hours in nitrogen atmosphere. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating way, and drying in vacuum to obtain 28.2 mg of yellow oil-drop 2-phenyl-4, 5-dihydro-3H-naphthoazepine with the yield of 52%.¹H NMR (500 MHz, CDCl₃) δ 8.34 (d, J = 8.0 Hz, 1H), 8.19-8.18 (m, 2H), 7.84 (d, J = 7.5 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.53-7.48 (m, 5H), 7.36 (d, J = 8.0 Hz, 1H), 2.72-2.68 (m, 4H), 2.58-2.53 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 171.6, 144.8, 139.3, 133.2, 130.4, 129.0, 128.6, 127.7, 127.5, 127.3, 126.7, 125.45, 125.37, 124.4, 124.0, 36.5, 30.7, 29.2。

The specific embodiment twenty three: 2-bromoaniline (0.2 mmol), 1- (2-methyl) phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, rotatably removing the solvent from the combined effluent by using the rotary evaporator, and drying in vacuum to obtain yellow solid oil drops of 35.7 mg of 2- (2-methyl) phenyl-4, 5-dihydro-3H-benzazepine with the yield of 76%.¹H NMR (500 MHz, CDCl₃) δ 7.44-7.42 (m, 1H), 7.31-7.23 (m, 4H), 7.20-7.16 (m, 2H), 7.08 (t, J = 7.0 Hz, 1H), 2.65 (t, J = 7.0 Hz, 2H), 2.53-2.50 (m, 5H), 2.40-2.35 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 175.3, 149.3, 141.4, 135.3, 131.2, 131.0, 128.8, 128.7, 127.9, 127.2, 125.8, 124.7, 124.0, 34.6, 32.6, 30.5, 20.6。

The specific embodiment twenty four: 2-bromoaniline (0.2 mmol), 1- (4-methyl) phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating way, and drying in vacuum to obtain 40.4 mg of yellow oil drop 2- (4-methyl) phenyl-4, 5-dihydro-3H-benzazepine with the yield of 86%.¹H NMR (500 MHz, CDCl₃) δ 7.90 (d, J = 8.0 Hz, 2H), 7.31-7.25 (m, 3H), 7.18-7.15 (m, 2H), 7.07-7.03 (m, 1H), 2.62 (t, J = 7.5 Hz, 2H), 2.53 (t, J = 7.0 Hz, 2H), 2.41 (s, 3H), 2.39-2.33 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 171.2, 150.0, 140.7, 136.4, 131.4, 129.2, 128.7, 127.19, 127.15, 124.4, 123.8, 34.5, 30.3, 28.7, 21.4。

The specific embodiment is twenty five: 2-bromoaniline (0.2 mmol), 1- (3, 5-dimethyl) phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg、）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with rotary evaporator to obtain residue, passing the residue through silica gel column, eluting with ethyl acetate and petroleumEluting the eluent prepared by the ether according to the volume ratio of 1:60, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent by using a rotary evaporator, and drying in vacuum to obtain yellow oil drops of 36.9 mg of 2- (3, 5-dimethyl) phenyl-4, 5-dihydro-3H-benzazepine with the yield of 74%.¹H NMR (500 MHz, CDCl₃) δ 7.62 (s, 2H), 7.33-7.30 (m, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.13 (s, 1H), 7.09-7.06 (m, 1H), 2.64 (t, J = 7.0 Hz, 2H), 2.56 (t, J = 7.5 Hz, 2H), 2.41-2.36 (m, 8H). ¹³C NMR (125 MHz, CDCl₃) δ 171.8, 149.9, 139.2, 138.0, 132.1, 131.3, 128.7, 127.1, 125.0, 124.4, 123.8, 34.6, 30.3, 28.9, 21.3。

Specific example twenty-six: 2-bromoaniline (0.2 mmol), 1- (4-tert-butyl) phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating way, and drying in vacuum to obtain 41.0 mg of yellow oil drop 2- (4-tert-butyl) phenyl-4, 5-dihydro-3H-benzazepine with the yield of 74%.¹H NMR (500 MHz, CDCl₃) δ 7.97 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.32 (t, J = 7.5 Hz, 1H), 7.19 (d, J = 7.0 Hz, 2H), 7.08 (t, J = 7.5 Hz, 1H), 2.65 (t, J = 7.0 Hz, 2H), 2.56 (t, J = 7.0 Hz, 2H), 2.41-2.36 (m, 2H), 1.38 (s, 9H). ¹³C NMR (125 MHz, CDCl₃) δ 171.2, 153.9, 150.0, 136.2, 131.4, 128.7, 127.2, 127.0, 125.5, 124.4, 123.9, 34.8, 34.5, 31.2, 30.3, 28.6。

The specific embodiment is twenty-seven: 2-bromoaniline (0.2 mmol), 1- (4-methoxy) phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent from the combined effluent by using a rotary evaporator in a rotating way, and drying in vacuum to obtain 33.1 mg of yellow oil-drop 2- (4-methoxy) phenyl-4, 5-dihydro-3H-benzazepine with the yield of 66%.¹H NMR (500 MHz, CDCl₃) δ 8.00-7.98 (m, 2H), 7.30 (td, J = 7.5, 1.0 Hz, 1H), 7.17 (t, J = 7.5 Hz, 2H), 7.06 (td, J = 7.5, 1.0 Hz, 1H), 6.99-6.97 (m, 2H), 3.87 (s, 3H), 2.63 (t, J = 7.5 Hz, 2H), 2.54 (t, J = 7.5 Hz, 2H), 2.39-2.33 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 170.5, 161.6, 150.1, 131.7, 131.3, 128.9, 128.7, 127.1, 124.2, 123.8, 113.8, 55.4, 34.3, 30.3, 28.5。

The specific embodiment twenty eight: 2-bromoaniline (0.2 mmol), 1- (3-methoxy) phenylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with rotary evaporator to obtain residue, eluting the residue with silica gel column with eluent prepared from ethyl acetate and petroleum ether at volume ratio of 1:60, collecting eluate according to actual gradient, detecting by TLC,and combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the combined effluent by using a rotary evaporator, and drying in vacuum to obtain yellow oil drops of 30.1 mg of 2- (3-methoxy) phenyl-4, 5-dihydro-3H-benzazepine with the yield of 60%.¹H NMR (500 MHz, CDCl₃) δ 7.62 (s, 1H), 7.54 (d, J = 7.5 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H), 7.20-7.17 (m, 2H), 7.09-7.02 (m, 2H), 3.90 (s, 3H), 2.63 (t, J = 7.5 Hz, 2H), 2.55 (t, J = 7.0 Hz, 2H), 2.41-2.36 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 171.2, 159.9, 149.8, 140.6, 131.3, 129.4, 128.8, 127.2, 124.6, 123.8, 119.8, 116.6, 112.0, 55.4, 34.6, 30.3, 28.9。

Specific example twenty-nine: 2-bromoaniline (0.2 mmol), 1- (5-benzo [ b ], [ 2-bromoaniline (0.2 mmol) ]d][1,3]Dioxolane) cyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with a rotary evaporator to obtain residue, eluting the residue with silica gel column with eluent prepared from ethyl acetate and petroleum ether at a volume ratio of 1:60, collecting eluate according to actual gradient, detecting by TLC, mixing the eluates containing the target product, removing solvent from the combined eluate by rotary evaporator, and vacuum drying to obtain yellow oil drop 2- (5-benzo [ alpha ]d][1,3]Dioxolane) -4, 5-dihydro-3H-benzazepine 39.2 mg, 74% yield.¹H NMR (500 MHz, CDCl₃) δ 7.61 (s, 1H), 7.47 (dd, J= 8.0, 1.0 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 7.18-7.13 (m, 2H), 7.05 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 8.0 Hz, 1H), 6.03 (s, 2H), 2.59 (t, J = 7.0 Hz, 2H), 2.53 (t, J = 7.0 Hz, 2H), 2.38-2.32 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 170.3, 149.9, 149.7, 148.2, 133.7, 131.3, 128.7, 127.2, 124.4, 123.8, 122.1, 107.9, 107.3, 101.5, 34.4, 30.3, 28.7。

Thirty of the specific embodiments: 2-bromoaniline (0.2 mmol), 1- (4-fluorophenyl) cyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent by using a rotary evaporator in a rotating way on the combined effluent, and drying in vacuum to obtain 33.5 mg of yellow solid 2- (4-fluorophenyl) -4, 5-dihydro-3H-benzazepine, wherein the yield is 70%.¹H NMR (500 MHz, CDCl₃) δ 8.03-8.00 (m, 2H), 7.32 (td, J = 7.5, 1.0 Hz, 1H), 7.20-7.13 (m, 4H), 7.08 (td, J = 7.5, 1.0 Hz, 1H), 2.62 (t, J = 7.5 Hz, 2H), 2.55 (t, J = 7.5 Hz, 2H), 2.41-2.35 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 170.1, 164.3 (¹ J = 249.3 Hz), 149.7, 135.3 (⁴ J = 3.0 Hz), 131.2, 129.3 (³ J = 8.5 Hz), 128.8, 127.2, 124.6, 123.8, 115.4 (² J = 21.5 Hz), 34.4, 30.3, 28.7. ¹⁹F NMR (470 MHz, CDCl₃) δ -110.384 (s, 1F)。

The specific embodiment is thirty-one: 2-bromoaniline (0.2 mmol), 1- (4-chlorophenyl) cyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with rotary evaporator to obtain residue, and introducing the residueEluting the mixture by a silica gel column with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent by a rotary evaporator, and drying in vacuum to obtain 29.1 mg of yellow solid 2- (4-chlorophenyl) -4, 5-dihydro-3H-benzazepine with the yield of 57%.¹H NMR (500 MHz, CDCl₃) δ 7.95 (d, J = 8.5 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 7.32 (td, J = 7.5, 1.0 Hz, 1H), 7.20-7.15 (m, 2H), 7.08 (td, J = 7.5, 1.0 Hz, 1H), 2.61 (t, J = 7.5 Hz, 2H), 2.54 (t, J = 7.5 Hz, 2H), 2.41-2.35 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 170.2, 149.6, 137.5, 136.6, 131.2, 128.8, 128.7, 128.5, 127.3, 124.7, 123.8, 34.5, 30.3, 28.6。

The specific embodiment is thirty-two: 2-bromoaniline (0.2 mmol), 1- (3-trifluoromethylphenyl) cyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg) 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent by using the rotary evaporator to rotate the combined effluent, and drying in vacuum to obtain 49.7 mg of yellow oil drop 2- (3-trifluoromethylphenyl) -4, 5-dihydro-3H-benzazepine with the yield of 86%.¹H NMR (500 MHz, CDCl₃) δ 8.29 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.5 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.22-7.19 (m, 2H), 7.11 (t, J = 7.5 Hz, 1H), 2.66 (t, J = 7.5 Hz, 2H), 2.56 (t, J = 7.5 Hz, 2H), 2.45-2.39 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 169.9, 149.4, 139.9, 131.2, 131.1 (² J = 32.3 Hz), 130.4, 129.0, 128.9, 127.3, 126.9 (³ J = 3.7 Hz), 125.0, 124.1 (¹ J = 270.8 Hz), 124.0 (³ J = 3.9 Hz), 123.9, 34.6, 30.3, 28.7. ¹⁹F NMR (470 MHz, CDCl₃) δ -62.599 (s, 3F)。

The specific embodiment is thirty-three: 2-bromoaniline (0.2 mmol), 1- (2-naphthyl) cyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent by using a rotary evaporator in a rotating way on the combined effluent, and drying in vacuum to obtain 51.5 mg of yellow solid 2- (2-naphthyl) -4, 5-dihydro-3H-benzazepine with the yield of 95%.¹H NMR (500 MHz, CDCl₃) δ 8.26 (s, 1H), 8.16 (dd, J = 8.5, 1.0 Hz, 1H), 7.84-7.76 (m, 3H), 7.44-7.40 (m, 2H), 7.23 (t, J = 7.5 Hz, 1H), 7.14-7.10 (m, 2H), 6.99 (t, J = 7.0 Hz,1H), 2.66 (t, J = 7.5 Hz, 2H), 2.48 (t, J = 7.5 Hz, 2H), 2.37-2.31 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 171.2, 150.0, 136.4, 134.4, 133.1, 131.3, 128.85, 128.79, 128.2, 127.7, 127.5, 127.2, 127.1, 126.4, 124.6, 124.3, 123.9, 34.6, 30.4, 28.7。

The specific embodiment is thirty-four: 2-bromoaniline (0.2 mmol) and 1- (4- [1, 1']-Biphenyl) cyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC stirring in a nitrogen atmosphereThe reaction was carried out for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with rotary evaporator to obtain residue, eluting the residue with silica gel column with eluent prepared from ethyl acetate and petroleum ether at volume ratio of 1:60, collecting eluate according to actual gradient, detecting by TLC, mixing the eluates containing the target product, removing solvent from the combined eluates with rotary evaporator, and vacuum drying to obtain yellow oil drop 2- (4- [1, 1']-biphenyl) -4, 5-dihydro-3H-benzazepine 27.9 mg, 47% yield.¹H NMR (500 MHz, CDCl₃) δ 8.01-7.99 (m, 2H), 7.62-7.56 (m, 4H), 7.40-7.37 (m, 2H), 7.31-7.28 (m, 1H), 7.25-7.22 (m, 1H), 7.12-7.10 (m, 2H), 7.01-6.97 (m, 1H), 2.60-2.57 (m, 2H), 2.50-2.46 (m, 2H), 2.34-2.27 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 170.9, 150.0, 143.2, 140.4, 137.9, 131.3, 128.9, 128.8, 127.73, 127.71, 127.2, 127.1, 124.6, 123.9, 34.6, 30.4, 28.7.。

The specific embodiment is thirty-five: 2-bromoaniline (0.2 mmol), 1- (2-thiophene) cyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, removing the solvent by using a rotary evaporator in a rotating way on the combined effluent, and drying in vacuum to obtain 27.2 mg of yellow oil drop 2- (2-thiophene) -4, 5-dihydro-3H-benzazepine with the yield of 60%.¹H NMR (500 MHz, CDCl₃) δ 7.52-7.49 (m, 2H), 7.29 (t, J = 7.5 Hz, 1H), 7.18-7.15 (m, 2H), 7.12-7.10 (m, 1H), 7.06 (t, J = 7.5 Hz, 1H), 2.65 (t, J = 7.5 Hz, 2H), 2.57 (t, J = 7.5 Hz, 2H), 2.40-2.34 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 165.8, 149.3, 145.8, 131.6, 130.4, 128.8, 128.3, 127.6, 127.2, 124.6, 124.2, 34.1, 30.3, 29.3.。

The specific embodiment is thirty-six: 2-bromoaniline (0.2 mmol), 1, 3-diphenylcyclobutanol (0.22 mmol) and PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, leaching the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:60, collecting an effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluents containing a target product, rotatably removing the solvent from the combined effluent by using the rotary evaporator, and drying in vacuum to obtain 53.5 mg of yellow oil drops, 2, 4-diphenyl-4, 5-dihydro-3H-benzazepine and the yield of 90%.¹H NMR (500 MHz, CDCl₃) δ 7.94 (d, J = 7.0 Hz, 2H), 7.45-7.39 (m, 3H), 7.35 (t, J = 7.5 Hz, 1H), 7.27-7.18 (m, 6H), 7.13-7.07 (m, 2H), 3.88-3.84 (m, 1H), 3.01-2.96 (m, 2H), 2.83-2.72 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 169.9, 149.6, 144.8, 139.0, 130.5, 129.9, 129.7, 128.6, 128.5, 127.5, 127.4, 126.9, 126.8, 124.8, 124.3, 52.6, 37.5, 36.2.。

The specific embodiment is thirty-seven: 2-bromoaniline (0.2 mmol), 1-phenyl-3- (benzyloxy) methylcyclobutanol (0.22 mmol), PdCl₂（1.7mg）、PCy₃（5.6mg）、Cs₂CO₃(130.3mg), 4A MS (100.0mg) was added to ultra-dry toluene (2 mL) at 110^oC the reaction was stirred under nitrogen atmosphere for 12 hours. Filtering the reaction solution to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with rotary evaporator to obtain residue, passing the residue through silica gel column, and treating with acetic acidEluting ethyl ester and petroleum ether by using eluent prepared according to the volume ratio of 1:60, collecting effluent according to actual gradient, combining the effluent containing a target product through TLC detection, removing the solvent by rotating the combined effluent by using a rotary evaporator, and drying in vacuum to obtain yellow oil drops of 53.7 mg of 4- (benzyloxy) methyl-2-phenyl-4, 5-dihydro-3H-benzazepine with the yield of 79%.¹H NMR (500 MHz, CDCl₃) δ 8.11-8.09 (m, 2H), 7.52-7.46 (m, 3H), 7.42-7.33 (m, 6H), 7.22 (d, J = 7.5 Hz, 1H), 7.15 (d, J = 6.5 Hz, 1H), 7.09 (td, J = 7.0, 1.0 Hz, 1H), 4.57-4.50 (q, J = 10.0 Hz, 2H), 3.49-3.38 (m, 2H), 3.02-2.94 (m, 1H), 2.73-2.56 (m, 3H), 2.44-2.40 (m, 1H). ¹³C NMR (125 MHz, CDCl₃) δ 170.2, 149.6, 139.4, 138.2, 130.4, 129.5, 129.4, 128.5, 128.4, 127.7, 127.6, 127.3, 127.2, 124.5, 124.0, 73.2, 72.7, 47.2, 32.9, 31.0.。

In the embodiment of the invention, 2-halogenated aniline and aryl cyclobutanol are taken as reaction substrates, palladium chloride is taken as a catalyst, tricyclohexylphosphine is taken as a ligand, cesium carbonate is taken as alkali, ultra-dry toluene is taken as a solvent, and the reaction is carried out in the presence of 110 DEG C^oC the reaction was stirred under nitrogen atmosphere for 12 hours. In the first to third examples, X is used as a variable, and the result proves that the effect is best when X is a bromine atom. Examples four and five catalysts as variables, using PdCl₂The catalyst has the highest efficiency. Examples six and seven are based on base as variable, using Cs₂CO₃The effect is best when the product is used as alkali. Eight to ten examples were solvent variables, and the results demonstrated that ultra-dry toluene was the most suitable solvent. The eleventh and twelfth examples are variable in reaction temperature, and the reaction temperature is 110 deg.C^oThe highest yield was achieved at C. The thirteen to twenty-two embodiments are suitable in which the ortho-, meta-or para-position on the benzene ring is linked to an electron-withdrawing group or an electron-donating group, depending on the Ar in the 2-haloaniline, since the corresponding products are obtained in moderate to good yields. Examples twenty-three to thirty-five are variables where R' in the aryl cyclobutanol is substituted with different substituents. Examples thirty-six and thirty-seven are variables for R in aryl cyclobutanol and it is clear from the results that polysubstituted cyclobutanols are also compatible with this reaction.

According to the invention, the intermediate product does not need to be separated, the target product can be directly synthesized by simple raw materials, the process is simplified, the reaction condition is relatively mild, the energy consumption is low, the waste solution discharge is reduced, the environmental pollution is reduced, and the yield reaches up to 90%; in the above embodiment, 2-halogenated aniline containing different substituents and aryl cyclobutanol are selected as reactants, so that a series of 2-aryl benzazepine derivatives can be prepared, and the method has certain substrate universality and operation simplicity. The present invention is not limited to the above embodiments, and those skilled in the art can implement the present invention in other embodiments according to the disclosure of the present invention, or make simple changes or modifications on the design structure and idea of the present invention, and fall into the protection scope of the present invention.