Rapid preparation method and application of 3-aminoquinoline derivatives

Abstract

The present invention provides a method for rapidly preparing a 3-aminoquinoline derivative and its application. The structural formula of the 3-aminoquinoline derivative is shown in Formula (III): wherein, R<supgt;1< / supgt> is selected from C1-C6 alkyl or C6-C18 aryl; R<supgt;2< / supgt> is selected from C1-C5 alkyl; R<supgt;3< / supgt> is selected from hydrogen, alkoxy, halogen. The 3-aminoquinoline derivative of the present invention is constructed from simple raw materials in one step, with mild conditions, high atom economy, excellent yield, wide substrate scope, etc. Moreover, the post-treatment operation of this reaction is simple, and the 3-aminoquinoline derivative has tumor inhibitory activity.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a rapid preparation method and application of 3-aminoquinoline derivatives. Background Art

[0002] 3-Aminoquinoline derivatives are a class of nitrogen-containing heterocyclic compounds with important biological activities, widely present in natural products and bioactive molecules. For example, the drug AZD4901 containing a 3-aminoquinoline skeleton can be used to treat mental illness; the LdMetAP1 (Leishmania donovani methionine aminopeptidase 1) inhibitor QYT-4h can be used to effectively eliminate leishmaniasis; the BChE (butyrylcholinesterase) inhibitor S06-1011 not only plays a protective role in dementia but also plays a huge role in treatment and care (Bioorg. Med. Chem. 2016, 24, 3494; Chem. Biol. Drug Des. 2021, 97, 315; J. Med. Chem. 2021, 64, 6856; Bioorg. Med. Chem. 2003, 11, 2541; Carbohydr. Res. 2009, 344, 291.). Therefore, strategies for constructing 3-aminoquinoline compounds have been frequently reported.

[0003]

[0004] Although the synthesis of 3 - aminoquinoline compounds has been reported (Tetrahedron 2004, 60, 2937; Tetrahedron 2010, 60, 698; Chem. Commun. 2014, 50, 9588; Chem. Eur. J. 2014, 20, 7245; Org. Lett. 2014, 16, 2680; ACS Catal. 2015, 5, 4783; Chem. Commun. 2010, 46, 1769; J. Am. Chem. Soc. 1997, 119, 5591; Adv. Synth. Catal. 2013, 355, 627; Angew. Chem. Int. Ed. 2015, 54, 3773; J. Am. Chem. Soc. 2009, 131, 11049; J. Org. Chem. 2007, 72, 8146; Org. Lett. 2015, 17, 5934; Org. Lett. 2013, 15, 3734; Organometallics 2018, 37, 2941; Tetrahedron Lett. 2001, 42, 3251; Tetrahedron Lett. 1998, 39, 1313; Tetrahedron 2013, 69, 5092; Org. Lett. 2021, 23, 6789), these methods have various deficiencies in terms of step economy, atom economy, raw material availability, etc. The common problem among them is that the synthesis efficiency is relatively low.

[0005] Therefore, it is extremely necessary but challenging to develop a method for the efficient one - pot construction of 3 - aminoquinoline compounds starting from simple and readily available substrates under mild conditions, expand the structural diversity of products, and meet the drug activity research at more levels. Summary of the Invention

[0006] To solve the above - mentioned technical problems, the present invention provides a rapid preparation method and application of 3 - aminoquinoline derivatives. The 3 - aminoquinoline derivatives of the present invention are constructed in one step from simple raw materials, with mild conditions, high atom economy, excellent yields, a wide substrate range, etc. Generally, the reaction is completed within 10 minutes, and the post - treatment operation of this reaction is simple. The 3 - aminoquinoline derivatives synthesized in the present invention have antitumor activity. The "rapid" in the present invention means that the reaction of the present invention can be completed within 5 min - 30 min, and even quickly completed within 5 min - 10 min.

[0007] The present invention is achieved through the following solutions:

[0008] The first object of the present invention is to provide a rapid preparation method of 3 - aminoquinoline derivatives, comprising the following steps:

[0009] React the compounds shown in formula (I) and formula (II) in an organic solvent under the action of a metal salt oxidant to obtain the 3 - aminoquinoline derivative shown in formula (III);

[0010]

[0011] wherein, R 1 is selected from C1 - C6 alkyl or C6 - C18 aryl;

[0012] R 2 is selected from C1 - C5 alkyl;

[0013] R 3 is selected from hydrogen, alkoxy, halogen.

[0014] In an embodiment of the present invention, the metal salt oxidant is selected from manganese acetylacetonate and / or manganese acetate dihydrate. Further, manganese acetylacetonate is preferably used.

[0015] In an embodiment of the present invention, the molar ratio of the compound shown in formula (I) to the compound shown in formula (II) is 10:0.1 - 20; further, preferably 10:0.1 - 5, 10:0.1 - 10, 10:10 - 20, etc., specifically: 10:0.1, 10:1, 10:2, 10:3, 10:4, 10:5, 10:6,

[0016] 15, 10:16, 10:17, 10:18, 10:19, 10:20, etc., or any value between any two numerical values.

[0017] In one embodiment of the present invention, the dosage of the metal salt oxidant is 0.1 mol% - 200 mol% (this value is the proportion of the metal salt oxidant in the total molar amount of all reaction raw materials). Further, it is preferably 0.1 mol% - 10 mol%, 0.1 mol% - 20 mol%, 0.1 mol% - 40 mol%, 10 mol% - 50 mol%, 50 mol% - 200 mol%, 0.1 mol%, 1 mol%, 2 mol%, 3 mol%, 4 mol%, 5 mol%, 6 mol%, 7 mol%, 8 mol%, 9 mol%, 10 mol%, 11 mol%, 12 mol%, 13 mol%, 14 mol%, 15 mol%, 16 mol%, 17 mol%, 18 mol%, 19 mol%, 20 mol%, 20 mol%, 30 mol%, 40 mol%, 50 mol%, 60 mol%, 70 mol%, 80 mol%, 90 mol%, 100 mol%, 150 mol%, 200 mol%, etc., or any value between any two values.

[0018] In one embodiment of the present invention, the organic solvent is selected from one or more of acetonitrile, 1,4 - dioxane, 1,2 - dichloroethane, water, ethanol, and toluene.

[0019] In one embodiment of the present invention, the reaction is carried out under the protection of an inert atmosphere.

[0020] Further, the gas in the inert atmosphere is an inert gas and / or nitrogen. The inert gas is selected from one or more of helium, neon, and argon.

[0021] In one embodiment of the present invention, the temperature of the reaction is 25°C - 80°C, and the reaction time is 5 min - 30 min. Preferably, the reaction time is 5 min - 10 min, 5 min - 20 min, 5 min - 30 min, etc., specifically 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min, 19 min, 20 min, 21 min, 22 min, 23 min, 24 min, 25 min, 26 min, 27 min, 28 min, 29 min, 30 min, etc., or any value between any two values.

[0022] The second object of the present invention is to provide a 3 - aminoquinoline derivative prepared by the described rapid preparation method, and the structural formula of the 3 - aminoquinoline derivative is:

[0023] Wherein, R1 Selected from C1-C6 alkyl or C6-C18 aryl;

[0024] R 2 Selected from C1-C5 alkyl;

[0025] R 3 Selected from hydrogen, alkoxy, halogen.

[0026] In one embodiment of the present invention, R 1 Selected from substituted or unsubstituted phenyl, thiophenyl; wherein the substituents on the substituted phenyl and thiophenyl are independently selected from one or more of hydrogen, C1-C5 alkyl, C1-C5 alkoxy, halogen, phenyl, cyano and ethoxycarbonyl.

[0027] Preferably, R 1 Selected from n-butyl, isopropyl, phenethyl, cyclopentenyl, thiophenyl, or substituted phenyl, wherein the substituents on the substituted phenyl are selected from hydrogen, methoxy, methyl, tert-butyl, phenyl, ethoxycarbonyl, cyano, fluorine, chlorine or bromine.

[0028] Preferably, R 2 Selected from ethyl.

[0029] Preferably, R 3 Selected from hydrogen, methoxy, bromine.

[0030] Preferably, the compounds represented by formula (I) are preferably selected from benzeneboronic acid (1), 4-methylbenzeneboronic acid (2), 4-methoxybenzeneboronic acid (3), 4-tert-butylbenzeneboronic acid (4), 4-(9H-carbazol-9-yl)benzeneboronic acid (5), 4-phenylbenzeneboronic acid (6), 4-fluorobenzeneboronic acid (7), 4-chlorobenzeneboronic acid (8), 4-bromobenzeneboronic acid (9), 4-cyanobenzeneboronic acid (10), 4-ethoxycarbonylbenzeneboronic acid (11), 2-methylbenzeneboronic acid (12), 3,4-dimethoxybenzeneboronic acid (13), 3,5-dimethylbenzeneboronic acid (14), 3-thiopheneboronic acid (15), n-butylboronic acid (16), phenethylboronic acid (17), isopropylboronic acid (18), cyclopentenylboronic acid (19).

[0031] The specific structural formulas of the compounds represented by formula (I) corresponding to the above numbers are as follows:

[0032]

[0033] Preferably, the compounds represented by formula (II) are preferably selected from o-isocyanobenzyl cyanide (20), 3-bromo-o-isocyanobenzyl cyanide (21), 3,4-dimethoxy-o-isocyanobenzyl cyanide (22), 2-(2-isocyanophenyl)butyronitrile (23), and the structural formulas are as follows:

[0034]

[0035] Preferably, the structural formula of the 3-aminoquinoline derivative shown in formula (III) is shown as one of formula (III-1) or formula (III-22):

[0036]

[0037] In one embodiment of the present invention, the alkyl group in the C1-C6 alkyl group or C1-C5 alkyl group is selected from a straight-chain alkyl group or a cycloalkyl group.

[0038] The third object of the present invention is to provide the use of the 3-aminoquinoline derivative in the preparation of an anti-tumor drug.

[0039] The reaction mechanism of the present invention is as follows:

[0040] Taking the reaction of a boric acid compound and o-isocyanoacetonitrile as raw materials and Mn(acac)3 as an oxidant as an example, in the preparation process of the 3-aminoquinoline derivative shown in formula (III) of the present invention, the reaction principle is as follows:

[0041]

[0042] First, boric acid generates a carbon radical A in the presence of Mn(III), and then intermediate A adds to the isocyanide compound to generate the corresponding imide radical B. Subsequently, the imide radical B undergoes a cycloaddition reaction with the cyano group to generate a cyclized imine radical C. Finally, radical C undergoes a hydrogen atom transfer (HAT) from the environment to obtain a cyclic imine D, and the cyclic imine D isomerizes to obtain the desired 3-aminoquinoline compound.

[0043] The present invention discovers that in DCE, Mn(acac)3 exhibits extremely high reaction performance at 60°C, while the activity of Mn(OAc)3·2H2O is much lower. By comparing the reaction time, temperature, solvent, and the redox potentials of the two manganese salts, it is found that Mn(acac)3 exhibits a higher current density than Mn(OAc)3·2H2O in the redox reaction, occupying a kinetic advantage, which is the main reason for the difference in their reaction activities.

[0044] The above technical solutions of the present invention have the following advantages compared with the prior art:

[0045] The present invention uses isocyanide and boric acid compound as reaction raw materials to prepare 3-aminoquinoline derivatives by a one-pot method. Compared with the prior art, the present invention provides a more step-economic, atom-economic, convenient post-treatment, rapid and efficient synthesis method of 3-aminoquinoline derivatives. This method is constructed in one step using simple raw materials, has the advantages of cheap and easily available raw materials, simple and mild conditions, high atom economy, excellent yield, with the highest yield up to 97%, and also has the advantages of a wide substrate range, etc., providing a very green synthesis method for the efficient construction of the 3-aminoquinoline skeleton.

[0046] The present invention provides a series of 3-aminoquinoline derivatives with potential biological activities, and the 3-aminoquinoline derivatives have the characteristics of potential anti-tumor activities. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] In order to make the content of the present invention easier to be clearly understood, the following further details the present invention according to the specific embodiments of the present invention in combination with the drawings, wherein

[0048] Figure 1 is the hydrogen nuclear magnetic resonance characterization spectrum of compound III-1 in Example 1 of the present invention;

[0049] Figure 2 is the carbon nuclear magnetic resonance characterization spectrum of compound III-1 in Example 1 of the present invention;

[0050] Figure 3 is the reaction influence of different manganese sources in the present invention;

[0051] Figure 4 is the reaction influence of different reaction temperatures in the present invention;

[0052] Figure 5 is the reaction influence of different reaction solvents in the present invention;

[0053] Figure 6 is the reaction influence of different manganese sources in terms of electrochemistry in the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0054] The following further illustrates the present invention in combination with the drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the examples given are not intended to limit the present invention.

[0055] The following embodiments of the present invention provide a preparation method of the quinoline derivative shown in one of Formulae (III-1) to (III-22) above. The numbers in the following raw materials correspond to the numbers above.

[0056] Example 1: Synthesis of the compound shown in (III-1)

[0057] Weigh 0.4 mmol of phenylboronic acid (the compound corresponding to No. (1), 0.0488 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g, 200 mol%) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with a mesh size of 200 - 300, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:20), and 0.0427 g of the reaction product is obtained.

[0058] Characterize the above reaction product, and the results are as follows:

[0059] 1 H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.7 Hz, 1H), 7.74 (d, J = 7.2 Hz, 2H), 7.64–7.58 (m, 1H), 7.52 (t, J = 7.3 Hz, 2H), 7.49–7.40 (m, 3H), 7.32 (s, 1H), 3.96 (s, 2H).

[0060] According to the characterization data, it can be known that the prepared reaction product is a pure product (purity > 95%); calculate the product yield, and the result is 97%.

[0061] Example 2: Synthesize the compound shown in (III-2)

[0062] Weigh 0.4 mmol of 4-methylphenylboronic acid (the compound corresponding to No. (2), 0.0544 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with a mesh size of 200 - 300, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0431 g of the reaction product is obtained.

[0063] Characterize the above reaction product, and the results are as follows:

[0064] 11H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.67–7.59 (m, 3H), 7.44 (q, J = 5.8 Hz, 2H), 7.33 (d, J = 8.4 Hz, 3H), 3.98 (s, 2H), 2.43 (s, 3H).

[0065] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 92%.

[0066] Example 3: Synthesis of the compound shown in (III-3)

[0067] Weighed 0.4 mmol of 4-methoxyphenylboronic acid (the compound corresponding to No. (3), 0.0608 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, added 2 mL of 1,2-dichloroethane as the solvent, and stirred the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction was completed, the reaction solution was subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase was silica gel powder with 200 - 300 mesh, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:30), and 0.0485 g of the reaction product was obtained.

[0068] The characterization of the above reaction product showed that:

[0069] 1 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.8 Hz, 1H), 7.71 (d, J = 8.2 Hz, 2H), 7.60 (d, J = 7.3 Hz, 1H), 7.46–7.39 (m, 2H), 7.29 (s, 1H), 7.04 (d, J = 8.2 Hz, 2H), 3.99 (s, 2H), 3.86 (s, 3H).

[0070] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 97%.

[0071] Example 4: Synthesis of the compound shown in (III-4)

[0072] Weigh 0.4 mmol of 4-tert-butylphenylboronic acid (the compound corresponding to No. (4), 0.0712 g), 0.2 mmol of o-isocyanobenzyl cyanide (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder of 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0508 g of the reaction product is obtained.

[0073] The above reaction product was characterized, and the results were as follows:

[0074] 1 H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.7 Hz, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 7.4 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.47–7.39 (m, 2H), 7.32 (s, 1H), 4.01 (s, 2H), 1.37 (s, 9H).

[0075] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 92%.

[0076] Example 5: Synthesis of the compound shown in (III-5)

[0077] Weigh 0.4 mmol of 4-(9H-carbazol-9-yl)phenylboronic acid (the compound corresponding to No. (5), 0.115 g), 0.2 mmol of o-isocyanobenzyl cyanide (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder of 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0709 g of the reaction product is obtained.

[0078] The above reaction product was characterized, and the results were as follows:

[0079] 11H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 7.6 Hz, 2H), 8.11–7.96 (m, 3H), 7.76 (d, J = 7.9 Hz, 2H), 7.66 (d, J = 7.6 Hz, 1H), 7.57–7.40 (m, 7H), 7.32 (t, J = 6.8 Hz, 2H), 4.10 (s, 2H).

[0080] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 92%.

[0081] Example 6: Synthesis of the compound shown in (III-6)

[0082] Weighed 0.4 mmol of 4-phenylphenylboronic acid (the compound corresponding to No. (6), 0.0792 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, added 2 mL of 1,2-dichloroethane as the solvent, and stirred the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction was completed, the reaction solution was subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase was silica gel powder of 200-300 mesh, the mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) was 1:30), and 0.0569 g of the reaction product was obtained.

[0083] The above reaction product was characterized, and the results were as follows:

[0084] 1 1H NMR (400 MHz, DMF) δ 7.98 (d, J = 8.1 Hz, 2H), 7.89 (d, J = 8.0 Hz, 3H), 7.84 (d, J = 7.5 Hz, 2H), 7.71 (d, J = 8.9 Hz, 1H), 7.58–7.53 (m, 3H), 7.47–7.41 (m, 3H), 5.49 (s, 2H).

[0085] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 96%.

[0086] Example 7: Synthesis of the compound shown in (III-7)

[0087] Weigh 0.4 mmol of 4-fluorophenylboronic acid (the compound corresponding to No. (7), 0.0592 g), 0.2 mmol of o-isocyanobenzyl cyanide (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react for 10 minutes under an argon atmosphere at 60 °C. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0429 g of the reaction product is obtained.

[0088] Characterize the above reaction product, and the results are as follows:

[0089] 1 H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.6 Hz, 1H), 7.81–7.69 (m, 2H), 7.62 (d, J = 9.1 Hz, 1H), 7.50–7.39 (m, 2H), 7.34 (s, 1H), 7.21 (t, J = 8.6 Hz, 2H), 3.95 (s, 2H).

[0090] According to the characterization data, it can be known that the prepared reaction product is a pure product (purity > 95%); calculate the product yield, and the result is 90%.

[0091] Example 8: Synthesis of the compound shown in (III-8)

[0092] Weigh 0.4 mmol of 4-chlorophenylboronic acid (the compound corresponding to No. (8), 0.0624 g), 0.2 mmol of o-isocyanobenzyl cyanide (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react for 10 minutes under an argon atmosphere at 60 °C. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0442 g of the reaction product is obtained.

[0093] Characterize the above reaction product, and the results are as follows:

[0094] 11H NMR (400 MHz, DMSO) δ 7.79 (t, J = 7.7 Hz, 3H), 7.65 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 8.5 Hz, 2H), 7.45–7.34 (m, 3H), 5.37 (s, 2H).

[0095] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 87%.

[0096] Example 9: Synthesis of the compound shown in (III-9)

[0097] Weigh 0.4 mmol of 4-bromophenylboronic acid (the compound corresponding to No. (9), 0.080 g), 0.2 mmol of o-isocyanobenzyl cyanide (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0507 g of the reaction product is obtained.

[0098] The above reaction product was characterized, and the results were as follows:

[0099] 1 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 10.8 Hz, 5H), 7.45 (s, 2H), 7.34 (s, 1H), 3.91 (s, 2H).

[0100] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 85%.

[0101] Example 10: Synthesis of the compound shown in (III-10)

[0102] Weigh 0.4 mmol of 4-cyanophenylboronic acid (the compound corresponding to No. (10), 0.0588 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0353 g of the reaction product is obtained.

[0103] The above reaction product was characterized, and the results were as follows:

[0104] 1 H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.2 Hz, 1H), 7.93 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 6.8 Hz, 1H), 7.52–7.42 (m, 2H), 7.39 (s, 1H), 3.95 (s, 2H).

[0105] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 72%.

[0106] Example 11: Synthesis of the compound shown in (III-11)

[0107] Weigh 0.4 mmol of 4-ethoxycarbonylphenylboronic acid (the compound corresponding to No. (11), 0.0776 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0409 g of the reaction product is obtained.

[0108] The above reaction product was characterized, and the results were as follows:

[0109] 11H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.0 Hz, 2H), 8.02 (d, J = 7.5 Hz, 1H), 7.85 (d, J = 8.0 Hz, 2H), 7.66–7.60 (m, 1H), 7.50–7.42 (m, 2H), 7.37 (s, 1H), 4.42 (q, J = 7.1 Hz, 2H), 1.43 (t, J = 7.1 Hz, 3H).

[0110] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 70%.

[0111] Example 12: Synthesis of the compound shown in (III-12)

[0112] Weigh 0.4 mmol of 2-methylphenylboronic acid (the compound corresponding to No. (12), 0.0544 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder of 200-300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0375 g of the reaction product is obtained.

[0113] The characterization of the above reaction product shows that:

[0114] 1 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 6.9 Hz, 1H), 7.50 (d, J = 8.2 Hz, 1H), 7.37–7.30 (m, 2H), 7.22 (s, 4H), 7.15 (s, 1H), 3.62 (s, 2H), 2.08 (s, 3H).

[0115] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 80%.

[0116] Example 13: Synthesis of the compound shown in (III-13)

[0117] Weigh 0.4 mmol of 3,4-dimethoxyphenylboronic acid (the compound corresponding to No. (13), 0.0728 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0538 g of the reaction product is obtained.

[0118] The above reaction product was characterized, and the results were as follows:

[0119] 1 H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.8 Hz, 1H), 7.59 (d, J = 7.4 Hz, 1H), 7.47–7.38 (m, 2H), 7.31 (t, J = 7.6 Hz, 3H), 6.97 (d, J = 8.1 Hz, 1H), 3.94 (s, 3H), 3.93 (s, 3H).

[0120] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 96%.

[0121] Example 14: Synthesis of the compound shown in (III-14)

[0122] Weigh 0.4 mmol of 3,5-dimethylphenylboronic acid (the compound corresponding to No. (14), 0.060 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0461 g of the reaction product is obtained.

[0123] The above reaction product was characterized, and the results were as follows:

[0124] 11H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.7 Hz, 1H), 7.60 (d, J = 8.9 Hz, 1H), 7.48–7.37 (m, 2H), 7.31 (s, 3H), 7.08 (s, 1H), 3.88 (s, 2H), 2.38 (s, 6H).

[0125] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield is calculated, and the result is 93%.

[0126] Example 15: Synthesis of the compound shown in (III-15)

[0127] Weigh 0.4 mmol of 3-thiopheneboronic acid (the compound corresponding to No. (15), 0.0512 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder of 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0366 g of the reaction product is obtained.

[0128] Characterize the above reaction product, and the results are as follows:

[0129] 1 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0 Hz, 1H), 7.90–7.85 (m, 1H), 7.65–7.58 (m, 2H), 7.51–7.41 (m, 3H), 4.11 (s, 2H).

[0130] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield is calculated, and the result is 81%.

[0131] Example 16: Synthesis of the compound shown in (III-16)

[0132] Weigh 0.4 mmol of n-butylboronic acid (the compound corresponding to No. (16), 0.0408 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 80 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder of 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0212 g of the reaction product is obtained.

[0133] The above reaction product was characterized, and the results were as follows:

[0134] 1 H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.2 Hz, 1H), 7.56 (d, J = 8.9 Hz, 1H), 7.47–7.31 (m, 2H), 7.20 (s, 1H), 3.85 (s, 2H), 2.95–2.85 (m, 2H), 1.86–1.76 (m, 2H), 1.56–1.45 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H).

[0135] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 53%.

[0136] Example 17: Synthesis of the compound shown in (III-17)

[0137] Weigh 0.4 mmol of phenethylboronic acid (the compound corresponding to No. (17), 0.060 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 80 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder of 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0442 g of the reaction product is obtained.

[0138] The above reaction product was characterized, and the results were as follows:

[0139] 11H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.47–7.37 (m, 2H), 7.35–7.22 (m, 5H), 7.18 (s, 1H), 3.66 (s, 2H), 3.23–3.19 (m, 2H), 3.18–3.13 (m, 2H).

[0140] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield is calculated, and the result is 89%.

[0141] Example 18: Synthesis of the compound shown in (III-18)

[0142] Weigh 0.4 mmol of isopropylboronic acid (the compound corresponding to No. (18), 0.0352 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0290 g of the reaction product is obtained.

[0143] Characterize the above reaction product, and the results are as follows:

[0144] 1 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.3 Hz, 1H), 7.60–7.52 (m, 1H), 7.45–7.34 (m, 2H), 7.19 (s, 1H), 3.87 (s, 2H), 3.27–3.17 (m, 1H), 1.43 (s, 3H), 1.41 (s, 3H).

[0145] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield is calculated, and the result is 78%.

[0146] Example 19: Synthesis of the compound shown in (III-19)

[0147] Weigh 0.4 mmol of cyclopentenylboronic acid (the compound corresponding to No. (19), 0.0448 g), 0.2 mmol of o-isocyanoacetophenone (the compound corresponding to No. (20), 0.0284 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react for 10 minutes under an argon atmosphere at 60 °C. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0395 g of the reaction product is obtained.

[0148] The above reaction product was characterized, and the results were as follows:

[0149] 1 H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.46–7.28 (m, 2H), 7.22 (s, 1H), 6.39 (s, 1H), 4.10 (s, 2H), 3.00 (t, J = 6.1 Hz, 2H), 2.66 (s, 2H), 2.11–2.00 (m, 2H).

[0150] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 94%.

[0151] Example 20: Synthesis of the compound shown in (III-20)

[0152] Weigh 0.4 mmol of phenylboronic acid (the compound corresponding to No. (1), 0.0488 g), 0.2 mmol of 3-bromo-o-isocyanoacetophenone (the compound corresponding to No. (21), 0.0440 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react for 10 minutes under an argon atmosphere at 60 °C. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0417 g of the reaction product is obtained.

[0153] The above reaction product was characterized, and the results were as follows:

[0154] 11H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.77–7.68 (m, 3H), 7.55–7.43 (m, 4H), 7.17 (s, 1H), 4.05 (s, 2H) ppm.

[0155] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield is calculated, and the result is 70%.

[0156] Example 21: Synthesis of the compound shown in (III-21)

[0157] Weigh 0.4 mmol of phenylboronic acid (the compound corresponding to No. (1), 0.0488 g), 0.2 mmol of 3,4-dimethoxy-o-isocyanoacetophenone (the compound corresponding to No. (22), 0.0404 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube, add 2 mL of 1,2-dichloroethane as the solvent, and stir and react at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (column chromatography separation conditions: the stationary phase is silica gel powder with 200-300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0476 g of the reaction product is obtained.

[0158] The characterization of the above reaction product shows that:

[0159] 1 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.1 Hz, 2H), 7.50 (t, J = 7.4 Hz, 2H), 7.43 (d, J = 7.6 Hz, 1H), 7.37 (s, 1H), 7.23 (s, 1H), 6.86 (s, 1H), 3.98 (s, 3H), 3.96 (s, 3H).

[0160] According to the characterization data, the obtained reaction product is a pure product (purity > 95%); the product yield is calculated, and the result is 85%.

[0161] Example 22: Synthesis of the compound shown in (III-22)

[0162] Weigh 0.4 mmol of phenylboronic acid (the compound corresponding to No. (1), 0.0488 g), 0.2 mmol of 2-(2-isocyanophenyl)butyronitrile (the compound corresponding to No. (23), 0.0340 g), and 0.4 mmol of Mn(acac)3 (0.1409 g) into a 25 mL Schlenk tube. Add 2 mL of 1,2-dichloroethane as the solvent and stir the reaction at 60 °C under an argon atmosphere for 10 minutes. After the reaction is completed, the reaction solution is subjected to vacuum evaporation and column chromatography separation (conditions for column chromatography separation: the stationary phase is silica gel powder with 200 - 300 mesh, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A:B) is 1:30), and 0.0471 g of the reaction product is obtained.

[0163] The above reaction product was characterized, and the results were as follows:

[0164] 1 H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.0 Hz, 1H), 7.75 (d, J = 7.3 Hz, 1H), 7.60 (d, J = 7.2 Hz, 2H), 7.53–7.19 (m, 5H), 3.83 (s, 2H), 2.86 (q, J = 7.5 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H).

[0165] According to the characterization data, the prepared reaction product is a pure product (purity > 95%); the product yield was calculated, and the result was 95%.

[0166] Example 23: Biological activity test

[0167] According to relevant references (Eur. J. Med. Chem. 2007, 42, 344.), the present invention selected 10 compounds prepared in the above examples and performed toxicity tests on three human cancer cells using the MTT method, and at the same time used the drug Doxorubicin as a control for the toxicity test. The results are shown in Table 1. The results show that the compounds shown in Formula III-1, III-5, III-8, III-9, III-11, and III-20 exhibit low micromolar cytotoxicity; the compounds shown in Formula III-7, III-16, III-21, and III-22 are inactive (IC 50 > 100 μM). It is worth noting that the 3-aminoquinoline compounds III-1, III-5, III-11, and III-20 show stronger inhibitory effects on one or more human cancer cells (IC 50 value is lower than that of doxorubicin).

[0168] Table 1. Test results of the cytotoxicity (IC 50 , μM) of different compounds

[0169] HT-1080 HT-29 MDA-MB-231 III-1 2.90 4.68 10.7 III-5 1.48 2.14 9.3 III-7 >100 >100 >100 III-8 6.84 18.1 34.3 III-9 10.8 23.2 14.2 III-11 1.23 1.97 1.82 III-16 51.0 89.0 >100 III-20 1.84 2.82 2.89 III-21 23.8 >100 >100 III-22 51.1 94.9 >100 Doxorubicin 0.12 0.48 0.05

[0170] The above results indicate that the 3-aminoquinoline derivatives synthesized in this invention have the potential property of inhibiting cancer cell activity and can be prepared into anti-tumor drugs.

[0171] This invention verified the reaction conditions of different manganese sources, different reaction temperatures, etc. through a series of experiments, as follows:

[0172] 1. The reaction process and results are shown in Figure 3 :

[0173] It was found that when using Mn(acac)3 as the promoter, the reaction could be completed within 10 minutes at 60 °C in DCE (the liquid-phase yield was as high as 99%) ( Figure 3 a) in). However, when using Mn(OAc)3·2H2O, a similar effect could not be achieved and the reaction effect was poor.

[0174] 2. The influence of different reaction temperatures, the reaction process and results are shown in Figure 4 :

[0175] Taking the reaction temperature as a variable, the activity change of Mn(OAc)3·2H2O was investigated, and the results are as Figure 4 shown. It was found that at 60 °C, even if the reaction was extended to 8 hours, the reaction still could not occur smoothly. When the temperature was raised to 80 °C (100 °C) and the reaction was carried out for 10 minutes, the liquid-phase yield of the target product could reach 38% (22%), but when the reaction was extended to 8 hours, the liquid-phase yield did not increase. By comparing with the template reaction, it was found that increasing the reaction temperature could narrow the activity difference between the two manganese salts, but could not change the order of their activities. Therefore, temperature is not the fundamental reason for the activity difference between the two.

[0176] 3. The influence of different reaction solvents, the reaction process and results are shown in Figure 5 :

[0177] Furthermore, we investigated the influence of the solvent, and the results are as Figure 5As shown. From the results in the figure, it was found that in toluene (60 °C), using Mn(acac)3 as the reaction promoter and reacting for 10 minutes, the target product could be obtained with a liquid-phase yield of 98%. Using Mn(OAc)3·2H2O, the target product could only be obtained with a liquid-phase yield of 10%. In DMF (60 °C), using Mn(acac)3 as the reaction promoter and reacting for 10 minutes, the target product was obtained with a liquid-phase yield of 35%. Using Mn(OAc)3·2H2O, the target product could only be obtained with a liquid-phase yield of 15%. It can be seen from this that different solvents can affect the activity difference between the two manganese salts, but still cannot change the order of their activities. Therefore, the solvent is not the fundamental reason for the activity difference between the two.

[0178] 4. Research in electrochemistry, the results are shown in Figure 6 :

[0179] Finally, we investigated the electrochemical behavior of the two manganese salts, and the results are as Figure 6 shown. From Figure 6 it can be seen that compared with the blank solution, redox reactions occurred in the solutions with Mn(acac)3 and Mn(OAc)3·2H2O electrolytes added. From the potential point of view, the starting reduction reaction potential of Mn(acac)3 was about 60 mV lower than that of Mn(OAc)3·2H2O. From a thermodynamic perspective, Mn(OAc)3·2H2O was easier to be reduced than Mn(acac)3, but this was contrary to the experimental facts. However, after the reaction started, the reduction current of Mn(acac)3 was significantly higher than that of Mn(OAc)3·2H2O, and its peak current was about 2.2 times that of Mn(OAc)3·2H2O. That is, from a kinetic perspective, Mn(acac)3 was easier to obtain electrons, the reduction reaction rate was dominant, and the presented activity was higher. This was consistent with the experimental facts and also indicated that this reaction might be a kinetic control process. This might be the fundamental reason for the difference in the reaction activities of the two manganese salts.

[0180] Obviously, the above embodiments are only examples clearly described and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or alterations can be made based on the above description. It is not necessary and impossible to list all the implementation manners here. And the obvious changes or alterations derived therefrom are still within the protection scope of the present invention.

Claims

1. A rapid preparation method of 3 - aminoquinoline derivatives, characterized in that, Comprising the following steps: Weigh 0.4 mmol of phenylboronic acid, 0.2 mmol of 2-(2-isocyanophenyl)butyronitrile, and 0.4 mmol of Mn(acac)3 into a Schlenk tube, add 2 mL of 1,2-dichloroethane as a solvent, and stir and react under an argon atmosphere at 60 °C to obtain the 3-aminoquinoline derivative shown in III-22;

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