Pyrroloquinoxaline quinazoline derivative as well as synthesis method and application thereof

Abstract

The invention discloses a synthetic method and application of a pyrrolo-quinoxaline-quinazoline derivative, and belongs to the technical field of biological medicines and organic semiconductor materials. The derivative shows abundant chemical diversity and controllable physical, chemical and biological activities by adjusting substituent groups and heteroatoms, and meets the requirements of multiple fields; the pyrrolo-quinoxaline-quinazoline derivative has excellent fluorescence performance and high electron mobility, can improve the response speed and efficiency of a device, is helpful for improving the photoelectric conversion efficiency of a photoelectric device, is efficient and environment-friendly in synthesis method, extremely small in catalyst dosage, mild in reaction condition, short in reaction time and high in yield, and is suitable for industrial production. The production cost is remarkably reduced, the product purity is improved, the derivative has excellent fluorescence performance and high electron mobility, great potential is shown in the field of photoelectric conversion, and the device efficiency can be improved. Meanwhile, due to the unique biological activity, the polypeptide becomes a potential drug skeleton, and a new thought is provided for research and development of new drugs by designing adjustable and controllable target combination.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine and organic semiconductor materials, and specifically relates to a class of pyrroloquinoxaline and quinazoline derivatives and a synthesis method and application thereof. Background Art

[0002] Quinazoline is an important class of heterocyclic compounds, which are composed of pyrrole ring, quinoxaline ring and quinazoline ring. These heterocyclic rings are connected by specific chemical bonds to form a complex molecular skeleton. This structural feature makes this type of compound show unique advantages in physical and chemical properties, such as high stability and excellent carrier mobility. It is also often used as a skeleton of optoelectronic materials and has important applications in electroluminescent active materials and electrochemical sensors. However, as optoelectronic materials, the optoelectronic properties of quinazoline derivatives, such as carrier mobility and luminescence efficiency, still need to be improved. How to improve their optoelectronic properties through molecular structure design and material composites is a research hotspot in the field of optoelectronic materials. Based on the structural characteristics of quinazoline derivatives, they show certain biological activity in drugs with anticancer, antibacterial and antimalarial activities. However, their activity intensity and selectivity still need to be improved. How to optimize their biological activity through molecular structure design is an important research topic in the current field of medicinal chemistry.

[0003] There are many methods for the synthesis of quinazoline derivatives. The traditional multi-step synthesis method and the emerging catalytic synthesis method are both important synthetic strategies. The catalytic synthesis method has attracted much attention due to its high efficiency and environmental protection.

[0004] Metal catalytic synthesis method: Although metal catalysts such as palladium and iron have been used in the synthesis of quinazoline, for example, the iron-mediated reduction cyclization strategy reported by the Pal team is used to synthesize fused quinazoline derivatives from specific precursors, it is still necessary to develop more efficient and environmentally friendly catalyst systems to reduce the amount of catalyst, reduce production costs, and reduce the impact on the environment; non-metal catalytic synthesis methods have broad application prospects due to their environmental protection and low cost. However, the application of non-metal catalysts in quinazoline synthesis is still in its infancy. How to further explore the application of acidic and alkaline non-metal catalysts in quinazoline synthesis, optimize reaction conditions, and improve yield and purity have become the key issues to be solved in non-metal catalytic synthesis methods; one-pot reaction method and dehydrogenation condensation cyclization reaction method have attracted attention due to their high efficiency and simplicity. The method reported by Ju's research group for preparing polysubstituted quinoline by one-pot reaction of o-bromoaromatic ketone / aldehyde, ammonia water and aromatic aldehyde or primary alcohol catalyzed by CuCl simplifies the synthesis process and improves the reaction efficiency by continuously performing multiple steps in one reaction vessel. Chen's group and Professor Jiang Huanfeng's group reported the use of Ru3(CO) 12 / Xantphos catalyst system and Ru3(CO) 12 / Xantphos-catalyzed dehydrogenation condensation cyclization reaction of o-aminobenzyl alcohol and nitrile to synthesize quinazoline, using the combination of dehydrogenation reaction and condensation cyclization reaction to achieve the construction of quinazoline ring. However, in practical applications, the one-pot reaction method and the dehydrogenation condensation cyclization reaction method still have the problems of poor adaptability of different substrates in one-pot reaction and dehydrogenation condensation cyclization reaction, limiting the scope of reaction application, and low yield and purity of the product. Laha's team reduced and cyclized 2-nitrobenzenesulfonamide and aldehyde in series in the presence of sodium dithionite to synthesize 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide; Kempe's team announced a t-KOBu-catalyzed amination / cyclization reaction for the synthesis of quinazoline ring from 2,3-dihydro-1H-pyrimidine and aldehyde.

[0005] Although the above-mentioned synthetic methods of quinazoline derivatives have enriched the synthetic methods of quinazoline ring, these methods still have limitations, such as the need for excessive reducing agents, high reaction temperatures and long reaction times, the need to improve the synthetic efficiency, high production costs, and large environmental impacts. Therefore, developing more environmentally friendly and efficient methods to achieve efficient green synthesis of quinazoline and its derivatives and expand their applications is still an important direction of current research. Summary of the invention

[0006] In view of the technical problems that the stability and carrier efficiency of existing quinazoline and its derivatives need to be improved, and the synthesis method thereof has high reaction temperature, long reaction time and excessive reducing agent, which leads to complex synthesis process and high synthesis cost, the present invention aims to provide a class of pyrroloquinoxalinoquinazoline derivatives and their synthesis method and application.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] The present invention provides a class of pyrroloquinoxaline and quinazoline derivatives, the structural formula of the pyrroloquinoxaline and quinazoline derivatives is shown in Formula 1;

[0009]

[0010] Among them, R1 is selected from any one of methyl and hydrogen atom; R2 is selected from any one of hydrogen atom, chlorine atom, bromine atom, trifluoromethyl, cyano, tert-butyl and methyl; R3 is selected from any one of hydrogen atom, chlorine atom and methyl; R4 is selected from any one of hydrogen atom, methyl, nitro, chlorine atom, bromine atom, fluorine atom, methyl, hydroxyl and methoxy; R5 is selected from any one of hydrogen atom and bromine atom; X is selected from any one of carbon and nitrogen; Y is selected from any one of carbon and nitrogen; Z is selected from any one of carbon and nitrogen; E is selected from any one of carbon, nitrogen and oxygen.

[0011] Furthermore, the pyrroloquinoxaline and quinazoline derivatives have a structure as shown in Formula 2-17:

[0012]

[0013] The present invention provides a method for synthesizing the above-mentioned pyrroloquinoxalinoquinazoline derivative, comprising:

[0014] (1) preparing 2-(4,5-dihydropyrrolo[1,2-α]quinoxalin-4-yl)aniline compounds containing different substituents;

[0015] The structural formula of the 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compound is as follows: Wherein R1 is selected from any one of a methyl group, a hydrogen atom, a chlorine atom, a bromine atom, a trifluoromethyl group, a cyano group, and a tert-butyl group;

[0016] (2) dissolving the 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compound containing different substituents obtained in step (1) and an aromatic aldehyde compound in an organic solvent, adding an acidic catalyst in a mass percentage of 0.04% to 0.06%, cooling to room temperature and drying by spin drying, separating and purifying, and eluting to obtain a pyrroloquinoxaline and quinazoline derivative;

[0017] The aromatic aldehyde compound is any one of benzaldehyde, o-bromobenzaldehyde, m-bromobenzaldehyde, p-bromobenzaldehyde, o-nitrobenzaldehyde, o-chlorobenzaldehyde, o-fluorobenzaldehyde, furanaldehyde and thiophenealdehyde.

[0018] The 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compounds containing different substituents are 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline, 2-(7-bromo-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(7-cyano-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(7-trifluoromethyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(7-chloro-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(7-fluoro-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(7-methyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(7-tert-butyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(7-chloro-8-chloro-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, 2-(6-methyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline, the acidic catalyst is any one of acetic acid, trifluoroacetic acid, hydrochloric acid, p-toluenesulfonic acid and methanesulfonic acid.

[0019] The organic solvent is any one of dichloromethane, chloroform and dichloroethane.

[0020] The molar ratio of the 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compound containing different substituents to the aromatic aldehyde compound is 1-3:1-3.

[0021] The reaction temperature is 20°C to 40°C, and the reaction time is 0.5h to 1h.

[0022] The eluent used for separation and purification is a mixed solvent of petroleum ether and dichloromethane in a volume ratio of 2 to 15:1 or a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 2 to 15:1.

[0023] The above-mentioned pyrroloquinoxaline and quinazoline derivatives are used in the preparation of organic semiconductor materials, and the pyrroloquinoxaline and quinazoline derivatives are used as organic semiconductor receptor materials.

[0024] The application of the above-mentioned pyrroloquinoxaline and quinazoline derivatives in the preparation of drug skeletons.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The pyrroloquinoxaline and quinazoline derivatives disclosed in the present invention contain multiple variable substituents (such as R1, R2, R3, R4, R5) and heteroatoms (X, Y, Z, E) at different positions in their structures. The selection of these substituents and heteroatoms enables the derivatives to exhibit unique physical, chemical and biological activities, and therefore have potential application value in the fields of organic semiconductor materials, drug development, etc.

[0027] The invention discloses a method for synthesizing pyrroloquinoxaline and quinazoline derivatives. Through a two-step synthesis method, a class of pyrroloquinoxaline and quinazoline derivatives with diverse structures and unique properties are successfully prepared. The synthesis method has the advantages of easy availability of raw materials, mild reaction conditions, high yield, etc. Various pyrroloquinoxaline and quinazoline derivatives with different structures and properties can be synthesized by adjusting substituents and reaction conditions. The synthesis method of the invention has the advantages of small amount of acidic catalyst, significantly reducing the catalyst cost in the synthesis process, and reducing the catalytic efficiency in subsequent treatment. The yield of pyrroloquinoxaline and quinazoline derivatives is above 61%, and the highest is up to 95%. The melting point range of these derivatives is large, 141°C to 223°C, which provides the possibility of expanding their application range.

[0028] Further, the synthesis method of the present invention can be reacted at room temperature, and the room temperature reaction conditions not only reduce energy consumption, but also simplify laboratory operation and equipment requirements, and improve the operability and safety of the synthesis. This is particularly important for industrial production, and can greatly reduce production costs and operational risks; the reaction time is short, only 30 minutes are needed, and the fast reaction time means higher production efficiency, which helps to shorten the production cycle, quickly respond to market demand, and the short-time reaction is also more conducive to controlling the reaction process and reducing the generation of by-products; the reaction substrate compatibility is good, the yield is high, and the good substrate compatibility enables the synthesis method to be applied to the preparation of pyrroloquinoxaline and quinazoline derivatives of various structures, providing a rich compound library for the fields of medicinal chemistry and materials science. High yield ensures the economy and feasibility of the synthesis process.

[0029] The application of the pyrroloquinoxaline and quinazoline derivatives disclosed in the present invention, the specific substituents and heteroatoms are selected so that the derivatives show excellent fluorescence properties and have high electron mobility, which can improve the response speed and efficiency of the device; the conjugated system and fluorescence properties in the molecular structure make the derivatives show efficient photon absorption and electron transfer capabilities in the photoelectric conversion process, and show excellent electron transmission performance, photoelectric conversion efficiency and other characteristics, which is helpful to improve the photoelectric conversion efficiency of the photoelectric device; by changing the types and positions of the substituents and heteroatoms, the spectral response range of the derivatives can be adjusted to match the emission spectra of different light sources, and at the same time have good thermal stability and chemical stability, Therefore, in the field of organic semiconductors, especially as receptor materials, it shows great application potential, which is of great significance for the development of new photoelectric conversion devices, organic solar cells and organic light-emitting diodes (OLEDs); pyrroloquinoxaline and quinazoline derivatives have unique biological activity and can specifically bind to biomacromolecules such as enzymes, receptors, and DNA, thereby regulating biological processes such as cell signal transduction and gene expression. As drug skeletons, by introducing specific functional groups or changing the position of substituents, the binding mode and affinity of derivatives to targets can be regulated, thereby improving the selectivity and effectiveness of drugs to meet the needs of specific disease treatment and provide new ideas for new drug research and development. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 1, wherein A is the hydrogen spectrum; B is the carbon spectrum;

[0031] Figure 2 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 2, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0032] Figure 3 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 3, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0033] Figure 4 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 4, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0034] Figure 5 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 5, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0035] Figure 6 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 6, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0036] Figure 7is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 7, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0037] Figure 8 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 8, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0038] Fig. 9 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 9, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0039] Fig.10 is the nuclear magnetic resonance spectrum of the pyrroloquinoxalinoquinazoline derivative of Example 10, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0040] Fig.11 is the nuclear magnetic resonance spectrum of the pyrroloquinoxalinoquinazoline derivative of Example 11, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0041] Fig.12 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 12, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0042] Fig.13 is the nuclear magnetic resonance spectrum of the pyrroloquinoxalinoquinazoline derivative of Example 13, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0043] Fig.14 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 14, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0044] Fig.15 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 15, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0045] Fig.16 is the nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivative of Example 16, wherein A is the hydrogen spectrum and B is the carbon spectrum;

[0046] Fig.17 is the nuclear magnetic resonance spectrum of the compound in Example 17, wherein A is the hydrogen spectrum and B is the carbon spectrum.

[0047] Fig.18 The fluorescence performance test diagram of pyrroloquinoxaline and quinazoline derivatives, wherein A is a solid-state ultraviolet-visible spectrum diagram, and B is a solid-state fluorescence spectrum diagram.

[0048] Fig.19The fluorescence performance test diagram of pyrroloquinoxaline and quinazoline derivatives, wherein A is the fluorescence spectrum in different solvents, B is the CIE diagram, C is the fluorescence lifetime, and D is the cyclic voltammogram. DETAILED DESCRIPTION

[0049] The following will clearly and completely describe the concept of the present invention and the technical effects produced in combination with the embodiments, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by technicians in this field without creative work are all within the scope of protection of the present invention. The test methods used in the embodiments are all conventional methods unless otherwise specified; the materials, reagents, etc. used, unless otherwise specified, can all be reagents and materials obtained from commercial channels.

[0050] In the description of the present invention, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. The present invention is further described in detail below in conjunction with the accompanying drawings:

[0051] The 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compounds in Examples 1 to 16 were prepared according to the following method (Quan Liu, Wenquan Wang, Meng Liu. Recent Progress in the Catalytic Synthesis of Pyrrolo[1,2-α]quinoxaline. Asian J. Org. Chem 2023, 12(8), e202300277)

[0052] 10mmol of 2-nitroaniline A containing different substituents was added to a 100mL round-bottom flask, followed by the addition of 30mL of acetic acid and heating to dissolve, followed by the slow dropwise addition of 2,5-dimethoxytetrahydrofuran (12mmol), followed by the reaction at 120°C for 3-6h under reflux conditions, and the reaction was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction mixture was cooled to room temperature, the acetic acid in the mixture was neutralized with an aqueous NaHCO3 solution, and then the aqueous phase was extracted with dichloromethane (40mL×3), the dichloromethane phases were combined, anhydrous MgSO4 was added to dry the organic phase for 5h, and the dichloromethane was removed under reduced pressure to obtain a crude product of N-(2-nitrophenyl)pyrrole B containing different substituents.

[0053] The N-(2-nitrophenyl)pyrrole B containing different substituents in the previous step was dissolved in 40 mL of anhydrous ethanol in a 100 mL round-bottom flask, and then a reducing agent, sodium dithionite (4.0 equiv., 40 mmol), was added and stirred to disperse the sodium dithionite in the ethanol solution, and then 20 mL of distilled water was added to the round-bottom flask. After that, the reaction was refluxed at 90° C. for 2 to 5 hours, and the progress of the reaction was monitored by TLC. After the reaction was completed, the reaction mixture was filtered while hot to remove excess sodium dithionite solid, and the filtrate was concentrated under reduced pressure to obtain a solid residue, which was finally purified by column chromatography to obtain pure N-(2-aminophenyl)pyrrole C containing different substituents.

[0054] Under nitrogen protection, N-(2-aminophenyl)pyrrole (5.0 mmol) and 2-aminobenzaldehyde (1.0 equiv., 5.0 mmol) containing different substituents were added to a 50 mL sealed tube, and 15 mL of anhydrous ethanol was added for magnetic stirring, and then HOAc (0.2 equiv., 1.0 mmol) was added. Subsequently, the reaction mixture was heated to 85° C. and refluxed for 8 h, and the degree of reaction was monitored by TLC. After the reaction was completed, the reaction mixture was diluted with a saturated sodium chloride solution, and the precipitate was precipitated and filtered under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compound D containing different substituents, and the reaction formula was as follows:

[0055]

[0056] Example 1

[0057] A mixture of 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5 hours. After the reaction was completed, it was cooled to room temperature, dried by spin drying, and separated and purified by column chromatography. The eluent consisted of petroleum ether and dichloromethane in a volume ratio of 2:1 to obtain 58.7mg of 6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 84%), melting point 193-194°C.

[0058]

[0059] The nuclear magnetic resonance of the pyrroloquinoxaline and quinazoline derivatives of this example is shown in the attached figure. Figure 1 As shown, attached Figure 1 In the figure, A is the hydrogen nuclear magnetic resonance spectrum, and B is the carbon nuclear magnetic resonance spectrum. Figure 1 It can be seen that the nuclear magnetic resonance hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.55~7.47 (m, 4H), 7.46~7.38 (m, 3H), 7.38~7.30 (m, 1H), 7.12~7.01 (m, 2H), 6.97~6.81 (m, 2H), 6.73~6.61 (m, 1H), 6.55 (d, J=7.6Hz, 1H), 6.48 (d, J=4.5Hz, 1H), 6.36 (t, J=7.6Hz, 1H), 6.29 (t, J=3.2Hz, 1H), 6.13 (dd, J=3.4,1.4Hz, 1H), 5.14 (s, 1H); Analysis of carbon nuclear magnetic resonance spectrum: 13 C NMR (100 MHz, DMSO-d6) δ: 142.7, 142.5, 135.6, 129.1, 128.5, 128.3, 127.4, 127.2, 126.9, 125.5, 125.3, 120.6, 120.2, 116.0, 115.5, 115.4, 114.1, 110.3, 107.8, 65.7, 49.7; HRMS-ESI (m / z) theoretical value C24H20N3[M+H]+: 350.1652; measured value: 350.1642. It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivatives of this embodiment is as follows:

[0060] The present embodiment provides pyrroloquinoxaline and quinazoline derivatives with unique biological activity, which can specifically bind to biomacromolecules such as enzymes, receptors, and DNA, thereby regulating biological processes such as cell signal transduction and gene expression, and can be used as drug skeletons. Therefore, by introducing specific functional groups or changing the position of substituents, the binding mode and affinity of the derivatives to the target can be regulated, thereby improving the selectivity and effectiveness of the drug to meet the needs of specific disease treatment and provide new ideas for new drug research and development.

[0061] Example 2

[0062] A mixture of 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), o-bromobenzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents), the mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, dried by rotation, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 10:1. 58.7mg of 6-(2-bromophenyl)-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 85%) was obtained. The melting point was 179-180℃.

[0063] The nuclear magnetic resonance image of the pyrroloquinoxaline and quinazoline derivatives of this embodiment is shown in the attached figure. Figure 2 As shown, attached Figure 2 In the figure, A is the hydrogen nuclear magnetic resonance spectrum, and B is the carbon nuclear magnetic resonance spectrum. Figure 2 From the data, we can see that the hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.67 (d, J = 7.8 Hz, 1H), 7.57-7.44 (m, 4H), 7.39 (d, J = 8.3 Hz, 1H), 7.36-7.29 (m, 1H), 7.10 (t, J = 7.7 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 6.91-6.85 (m, 2H), 6.66 (d, J = 8.0 Hz, 1H), 6.54 (dd, J = 16.2, 6.1 Hz, 2H), 6.41 (t, J = 7.4 Hz, 1H), 6.29 (t, J = 3.1 Hz, 1H), 6.17 (d, J = 3.4 Hz, 1H), 5.19 (s, 1H); Carbon spectrum analysis: 13C NMR (100 MHz, DMSO-d6) δ: 142.6, 140.3, 134.9, 133.8, 130.6, 130.5, 128.7, 128.0, 127.0, 126.8, 125.4, 125.1, 122.4, 120.5, 120.0, 116.3, 115.7, 115.5, 113.8, 110.3, 108.0, 66.2, 49.3; HRMS-ESI (m / z) theoretical value C 24 H 19 BrN3[M+H] + :428.0757; Measured value: 428.0689; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0064]

[0065] Example 3

[0066] A mixture of 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), m-bromobenzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5 hours. After the reaction was completed, it was cooled to room temperature, dried by spin drying, and separated and purified by column chromatography. The eluent consisted of petroleum ether and dichloromethane in a volume ratio of 2:1 to obtain 55.7mg of 6-(3-bromophenyl)-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 65%), with a melting point of 141°C to 142°C.

[0067] The nuclear magnetic resonance spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Figure 3 As shown, attached Figure 3 In the figure, A is the H NMR spectrum, and B is the C NMR spectrum; H spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.60 (t, J = 1.8 Hz, 1H), 7.58-7.44 (m, 4H), 7.43-7.33 (m, 2H), 7.10-7.02 (m, 2H), 6.90 (ddd, J = 17.1, 7.8, 6.5 Hz, 2H), 6.67 (dd, J = 8.1, 1.1 Hz, 1H), 6.55-6.47 (m, 2H), 6.37 (td, J = 7.4, 1.2 Hz, 1H), 6.29 (t, J = 3.1 Hz, 1H), 6.19 (dd, J = 3.4, 1.5 Hz, 1H), 5.10 (s, 1H); Carbon spectrum analysis:13 CNMR (100 MHz, DMSO-d6) δ: 145.6, 142.1, 135.3, 131.5, 131.2, 130.2, 128.5, 127.2, 126.9, 126.5, 125.4, 125.3, 122.4, 120.8, 120.1, 116.3, 116.1, 115.6, 115.5, 114.2, 110.3, 108.065.3, 49.8; RMS-ESI (m / z) theoretical value C 24 H 19 BrN3[M+H] + :428.0757; Measured value: 428.0600; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0068]

[0069] Example 4

[0070] A mixture of 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents) and p-bromobenzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5 hours. After the reaction was completed, it was cooled to room temperature, dried by spin drying, and separated and purified by column chromatography. The eluent was composed of petroleum ether and dichloromethane in a volume ratio of 2:1 to obtain 55.7mg of 6-(4-bromophenyl)-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 80%), with a melting point of 183℃~184℃.

[0071] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Figure 4 As shown, attached Figure 4 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1H NMR (600MHz, CDCl3) δ: 7.49 (d, J = 8.5Hz, 2H), 7.43 (d, J = 8.3Hz, 2H), 7.30 (d, J = 7.9Hz, 1H),7.20(dd,J=2.6,1.3Hz,1H),7.13(d,J=8.1Hz,1H),7.05~6.98(m,2H),6.89(t,J= 7.6Hz,1H),6.77(d,J=7.6Hz,1H),6.63(d,J=8.0Hz,1H),6.55(t,J=7.4Hz,1H),6.36(t,J=3.1Hz,1H),6.27(s,1H),6.13(d,J=2.3Hz,1H),5.23(s,1H),4.74(s,1H); Carbon spectrum analysis: 13 C NMR (150 MHz, CDCl3) δ: 140.5, 140.4, 135.0, 131.9, 129.1, 128.3, 127.7, 127.3, 125.6, 124.8, 122.3, 121.3, 120.8, 118.0, 115.3, 115.2, 114.4, 110.0, 107.7, 66.1, 49.9; HRMS-ESI (m / z) theoretical value C 24 H 19 BrN3[M+H] + :428.0757; Measured value: 428.0755; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0072]

[0073] Example 5

[0074] A mixture of 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents) and o-nitrobenzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5 hours. After the reaction was completed, it was cooled to room temperature, dried by spin drying, and separated and purified by column chromatography. The eluent was composed of petroleum ether and dichloromethane in a volume ratio of 2:1 to obtain 68.6mg of 6-(2-nitrophenyl)-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 87%), with a melting point of 174℃~175℃.

[0075] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Figure 5 As shown, attached Figure 5 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.94 (d, J=7.7Hz, 1H), 7.80~7.72 (m, 2H), 7.64 (ddd, J=7.9, 5.3, 3.6Hz, 1H), 7.54~7.44(m,2H),7.43~7.35(m,1H),7.10(qd,J=5.8,1.4Hz,2H),7.01(d,J=5.3Hz,1H),6.96(td,J= 7.7,1.5Hz,1H),6.90(td,J=7.6,1.1Hz,1H),6.73(dd,J=8.1,1.2Hz,1H),6.49(dt,J=7.7,1.4Hz,1H),6.40(td,J=7.4,1.2Hz,1H),6.27(t,J=3.2Hz,1H),6.14(dd,J=3.4,1.5Hz,1H),4.89(s,1H); Carbon spectrum analysis: 13 C NMR (100 MHz, DMSO-d6) δ: 147.8, 141.8, 135.6, 134.6, 133.4, 130.6, 130.1, 128.7, 126.9, 126.9, 125.8, 125.3, 124.8, 121.0, 120.0, 116.8, 116.1, 115.6, 114.4, 110.3, 108.1, 62.7, 50.1; HRMS-ESI (m / z) theoretical value C 24 H 19 N4O2[M+H] + :395.1503; Measured value: 395.1484; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0076]

[0077] Example 6

[0078] A mixture of 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents) and o-chlorobenzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5 hours. After the reaction was completed, it was cooled to room temperature, dried by spin drying, and separated and purified by column chromatography. The eluent was composed of petroleum ether and dichloromethane in a volume ratio of 2:1 to obtain 65.3mg of 6-(2-chlorophenyl)-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 85%), with a melting point of 168°C to 169°C.

[0079] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxalinoquinazoline derivative of this example Figure 6 As shown, attached Figure 6 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.57-7.46 (m, 4H), 7.44-7.36 (m, 3H), 7.12-7.06 (m, 1H), 6.95 (td, J = 7.7, 1.6 Hz, 1H), 6.86 (td, J = 7.6, 1.4 Hz, 2H), 6.66 (dd, J = 8.1, 1.1 Hz, 1H), 6.61 (d, J = 4.8 Hz, 1H), 6.55 (d, J = 7.5 Hz, 1H), 6.40 (td, J = 7.4, 1.1 Hz, 1H), 6.28 (t, J = 3.2 Hz, 1H), 6.16 (dd, J = 3.4, 1.5 Hz, 1H), 5.19 (s, 1H); Carbon spectrum analysis: 13 C NMR (100 MHz, DMSO-d6) δ: 142.6, 139.0, 135.0, 132.2, 130.6, 130.4, 130.3, 128.7, 127.5, 127.0, 126.8, 125.5, 125.1, 120.5, 112.0, 116.3, 115.7, 115.6, 115.5, 113.9, 110.3, 108.0, 64.1, 49.3; HRMS-ESI (m / z) theoretical value C 24 H 19 ClN3[M+H] + :384.1262; Measured value: 384.1230; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0080]

[0081] Example 7

[0082] A mixture of 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), o-fluorobenzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, dried by spin drying, and separated and purified by column chromatography. The eluent was composed of petroleum ether and dichloromethane in a volume ratio of 2:1 to obtain 58.8mg of 6-(2-fluorophenyl)-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 80%), with a melting point of 180℃~181℃.

[0083] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Figure 7 As shown, attached Figure 7 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.55~7.36 (m, 5H), 7.31~7.19 (m, 2H), 7.13~7.04 (m, 1H), 6.95 (td, J=7.7, 1.6Hz, 1H), 6.92~6.85 (m, 2H), 6.74~6.65 (m, 2H), 6.56 (dt, J=7.6, 1.3Hz, 1H), 6.40 (td, J=7.4, 1.2Hz, 1H), 6.29 (t, J=3.2Hz, 1H), 6.17 (dd, J=3.5, 1.5Hz, 1H), 5.23 (s, 1H); Carbon spectrum analysis: 13 C NMR (100 MHz, DMSO-d6) δ: 159.6 (d, J = 247.4 Hz), 142.6, 135.0, 130.8 (d, J = 8.4 Hz), 130.2, 129.2 (d, J = 12.2 Hz), 128.6, 127.1, 126.8, 125.4, 125.2, 124.7 (d, J = 3.4 Hz), 120.6, 119.9, 116.5, 116.3 (d, J = 5.7 Hz), 115.9, 115.7, 115.46, 114.0, 110.3, 108.0, 61.4, 49.6; HRMS-ESI (m / z) theoretical value C 24 H 19 FN3[M+H] + :368.1558; Measured value: 368.1560; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0084]

[0085] Example 8

[0086] A mixture of 2-(7-bromo-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 74.5mg of 3-bromo-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 87%), with a melting point of 186℃~187℃.

[0087] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Figure 8 As shown, attached Figure 8 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR(500MHz,DMSO-d6)δ:7.56(d,J=2.1Hz,1H),7.51~7.47(m,2H),7.45(d,J=7.1Hz,2H) ,7.40(dd,J=8.5,6.7Hz,2H),7.37~7.31(m,1H),7.08(d,J=4.6Hz,1H),7.04(dd,J=8.5,2 .0Hz,1H),6.97~6.91(m,1H),6.71(dd,J=8.1,1.2Hz,1H),6.53~6.46(m,2H),6.36(td,J=7.4,1.2Hz,1H),6.29(t,J=3.2Hz,1H),6.16(dd,J=3.4,1.5Hz,1H),5.11(s,1H); Carbon spectrum analysis: 13C NMR (125MHz, DMSO-d6) δ: 142.3, 142.2, 137.1, 129.1, 128.7, 128.4, 127.3, 126.8, 126.5, 125.1, 123.0, 119.9, 118.7, 117.5, 117.3, 116.1, 115.7, 114.3, 110.7, 108.3, 65.8, 49.7; HRMS-ESI (m / z) theoretical value C24H19N3[M+H]+: 428.0757; measured value: 428.0720; it can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivatives of this embodiment is as follows:

[0088]

[0089] Example 9

[0090] A mixture of 2-(7-cyano-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents) and benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 41.2mg of 3-cyano-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 55%).

[0091] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig. 9 As shown, attached Fig. 9 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.76~7.68 (m, 2H), 7.58 (dd, J=3.0, 1.5Hz, 1H), 7.49 (d, J=8. 4Hz,2H),7.42(t,J=7.4Hz,2H),7.36(d,J=7.1Hz,1H),7.22(d,J=8.3Hz,1H),7.14(d, J=4.4Hz,1H),6.95(t,J=7.6Hz,1H),6.73(d,J=8.0Hz,1H),6.61(d,J=4.4Hz,1H),6.54(d,J=7.6Hz,1H),6.41–6.32(m,1H),6.21(dd,J=3.3,1.4Hz,2H),5.20(s,1H); Carbon spectrum analysis:13 C NMR (101 MHz, DMSO-d6) δ 142.3, 142.1, 136.0 130.0, 129.2, 128.7, 128.4, 127.3, 126.8, 126.2, 125.9, 125.5, 119.8, 117.5, 116.2, 116.1, 116.0, 114.3, 112.8, 111.3, 108.8, 65.9, 49.8; HRMS-ESI (m / z) theoretical value C 25 H 19 N4[M+H]+: 375.1604; Measured value: 375.1581; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0092]

[0093] Example 10

[0094] A mixture of 2-(7-trifluoromethyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain 79.3mg of 3-trifluoromethyl-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 95%), with a melting point of 192℃~193℃.

[0095] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig.10 As shown, attached Fig.10 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1H NMR (400MHz, DMSO-d6) δ7.84(d,J=1.7Hz,1H),7.70(d,J=8.3Hz,1H),7.59(dd,J=3.1,1.5 Hz,1H),7.47(d,J=7.1Hz,2H),7.42(t,J=7.3Hz,2H),7.38–7.33(m,2H),7.09(d,J=4.7Hz, 1H), 6.96 (td, J = 7.8, 1.6 Hz, 1H), 6.74 (dd, J = 8.1, 1.1 Hz, 1H), 6.58 (d, J = 4.6 Hz, 1H), 6.55–6.49 (m, 1H), 6.37 (dt, J = 6.3, 4.6 Hz, 2H), 6.23 (dd, J = 3.5, 1.4 Hz, 1H), 5.17 (s, 1H); Carbon spectrum analysis: 13 C NMR (101 MHz, DMSO-d6) δ 142.19, 141.94, 136.02, 130.73, 129.19, 128.76, 128.47, 127.34, 126.78, 125.65, 119.77, 119.56, 116.41, 116.37, 116.32, 114.58, 111.71, 109.14, 107.43, 65.88, 49.65; HRMS-ESI (m / z) theoretical value C 25 H 19 F3N3[M+H]+: 418.1526; Measured value: 418.1531; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0096]

[0097] Embodiment 11

[0098] A mixture of 2-(7-chloro-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents) and benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 69.1mg of 3-chloro-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 90%).

[0099] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig.11 As shown, attached Fig.11 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (500MHz, DMSO-d6) δ: 7.54 (d, J = 8.5 Hz, 1H), 7.50 (dd, J = 3.0, 1.5 Hz, 1H), 7.46-7.43 (m, 3H), 7.41 (t, J = 7.6 Hz, 2H), 7.37-7.31 (m, 1H), 7.07 (d, J = 4.6 Hz, 1H), 6.97-6.88 (m, 2H), 6.71 (dd, J = 8.1, 1.2 Hz, 1H), 6.53-6.46 (m, 2H), 6.36 (td, J = 7.4, 1.2 Hz, 1H), 6.29 (t, J = 3.2 Hz, 1H), 6.16 (dd, J = 3.5, 1.5 Hz, 1H), 5.11 (s, 1H); Carbon spectrum analysis: 13 C NMR (125 MHz, DMSO-d6) δ: 142.3, 142.2, 137.0, 129.4, 129.2, 128.7, 128.4, 127.3, 126.8, 126.1, 125.1, 120.1, 119.9, 116.9, 116.2, 116.0, 115.7, 114.3, 110.6, 108.2, 65.8, 49.7; HRMS-ESI (m / z) theoretical value C 24 H 19 N3[M+H] + :384.1262; Measured value: 384.1233; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0100]

[0101] Example 12

[0102] A mixture of 2-(7-fluoro-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, dried by spin drying, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain 61.7mg of 3-fluoro-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 84%), with a melting point of 187℃~188℃.

[0103] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig.12 As shown, attached Fig.12 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR(500MHz,DMSO-d6)δ7.54(dd,J=8.8,5.7Hz,1H),7.49–7.44(m,3H),7.41(t,J=7.5Hz,2H) ,7.37–7.31(m,1H),7.29(dd,J=12.0,2.7Hz,1H),7.03(d,J=4.7Hz,1H),6.93(td,J=7.7,1.6H z, 1H), 6.69 (ddd, J = 12.4, 8.2, 1.9 Hz, 2H), 6.51 (d, J = 7.6 Hz, 1H), 6.45 (d, J = 4.6 Hz, 1H), 6.37 (td, J = 7.4, 1.1 Hz, 1H), 6.27 (t, J = 3.2 Hz, 1H), 6.15 (dd, J = 3.4, 1.5 Hz, 1H), 5.10 (s, 1H); Carbon spectrum analysis: 13 C NMR (125 MHz, DMSO-d6) δ: 160.2 (d, J = 237.8 Hz), 142.3, 142.2, 137.4 (d, J = 10.2 Hz), 129.2, 128.6, 128.4, 127.3, 126.9, 125.0, 123.8, 120.0, 116.6 (d, J = 9.8 Hz), 116.2, 115.6, 114.4, 110.3, 107.9, 106.4 (d, J = 22.9 Hz), 103.8 (d, J = 27.9 Hz), 66.0, 49.7; HRMS-ESI (m / z) theoretical value C 24 H 19 FN3[M+H]+: 368.1558; Measured value: 368.1548; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0104]

[0105] Example 13

[0106] A mixture of 2-(7-methyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain 60.3mg of 3-methyl-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 83%), with a melting point of 189℃~190℃.

[0107] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig.13 As shown, attached Fig.13 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR(400MHz, DMSO-d6)δ:7.43(m,J=21.5,8.4,2.3Hz,6H),7.36~7.29(m,1H),7.22(d, J=1.7Hz,1H),7.00(d,J=4.6Hz,1H),6.92(td,J=7.8,1.6Hz,1H),6.68(dd,J=8.1,1.2 Hz, 2H), 6.51 (dt, J = 7.6, 1.3Hz, 1H), 6.46 (d, J = 4.5Hz, 1H), 6.34 (td, J = 7.4, 1.2Hz, 1H), 6.25 (t, J = 3.2Hz, 1H) 6.10 (dd, J = 3.4, 1.5Hz, 1H), 5.09 (s, 1H), 2.28 (s, 3H); Carbon spectrum analysis: 13 C NMR (100 MHz, DMSO-d6) δ: 142.8, 142.5, 135.4, 134.4, 129.1, 128.4, 128.3, 127.4, 126.9, 125.3, 125.0, 121.0, 120.3, 116.5, 116.0, 115.3, 115.1, 114.1, 110.0, 107.5, 65.6, 49.6, 21.6; HRMS-ESI (m / z) theoretical value C 22 H 25 N3[M+H]+: 364.1808; Measured value: 364.1802; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0108]

[0109] Embodiment 14

[0110] A mixture of 2-(7-tert-butyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents) and benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 65.7mg of 3-tert-butyl-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 81%).

[0111] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig.14 As shown, attached Fig.14 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.49 (d, J = 7.2 Hz, 2H), 7.42 (ddd, J = 11.6, 5.3, 2.4 Hz, 4H), 7.36-7.32 (m, 2H), 7.07 (d, J = 4.5 Hz, 1H), 6.95-6.84 (m, 2H), 6.72-6.66 (m, 1H), 6.54 (d, J = 7.6 Hz, 1H), 6.50 (d, J = 4.4 Hz, 1H), 6.39-6.30 (m, 1H), 6.26 (t, J = 3.2 Hz, 1H), 6.09 (dd, J = 3.5, 1.5 Hz, 1H), 5.13 (s, 1H), 1.29 (s, 9H); Carbon spectrum analysis: 13 C NMR (100 MHz, DMSO-d6) δ: 147.8, 142.8, 142.7, 135.0, 129.1, 128.4, 128.2, 127.4, 126.9, 125.5, 125.1, 120.1, 117.3, 115.9, 115.1, 114.9, 114.1, 113.1, 110.0, 107.5, 65.6, 49.9, 34.9, 31.7; HRMS-ESI (m / z) theoretical value C 28 H 28 N3[M+H] + :406.2278; Measured value: 406.2264; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0112]

[0113] Embodiment 15

[0114] A mixture of 2-(7-chloro-8-chloro-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain 51.0mg of 2,3-dichloro-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 61%), with a melting point of 222℃~223℃.

[0115] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig.15 As shown, attached Fig.15 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (400MHz, DMSO-d6) δ: 7.86 (s, 1H), 7.62 (s, 1H), 7.59 (dd, J = 3.1, 1.5Hz, 1H), 7.48~ 7.43(m,2H),7.40(t,J=7.4Hz,2H),7.36~7.31(m,1H),7.08(d,J=4.6Hz,1H),6.95(m,J =7.6,1.6Hz,1H),6.73(dd,J=8.1,1.2Hz,1H),6.50(dd,J=5.2,3.4Hz,2H),6.37(m,J=7.4,1.2Hz,1H),6.31(t,J=3.2Hz,1H),6.18(dd,J=3.4,1.4Hz,1H),5.13(s,1H); Carbon spectrum analysis: 13 C NMR (100 MHz, DMSO-d6) δ: 142.2, 141.9, 135.7, 129.2, 128.8, 128.5, 127.3, 127.2, 127.0, 126.8, 125.3, 122.2, 119.8, 117.7, 117.0, 116.3, 114.4, 111.1, 108.7, 66.0, 49.7; HRMS-ESI (m / z) theoretical value C 24 H 18 C l2N3[M+H]+: 418.0872; Measured value: 418.0862; It can be seen that the structural formula of the pyrroloquinoxaline and quinazoline derivative of this embodiment is as follows:

[0116]

[0117] Example 16

[0118] A mixture of 2-(6-methyl-4,5-dihydropyrrolo[1,2-a]quinoxaline-4-yl)aniline (0.24mmol, 1.20 equivalents), benzaldehyde (0.2mmol) and dichloromethane (2mL) was added to a scintillation vial (20mL). After adding trifluoroacetic acid (0.002mmol, 0.01 equivalents). Then, the reaction mixture was stirred at room temperature for 0.5h. After the reaction was completed, it was cooled to room temperature, spin-dried, and separated and purified by column chromatography. The eluent was composed of petroleum ether and ethyl acetate in a volume ratio of 15:1 to obtain 46.5mg of 1-methyl-6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (yield: 64%), with a melting point of 186℃~187℃.

[0119] The nuclear magnetic resonance hydrogen spectrum of the pyrroloquinoxaline and quinazoline derivatives of this example is as follows Fig.16 As shown, attached Fig.16 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR (400MHz, Chloroform-d) δ: 8.17 (s, 1H), 7.99-7.92 (m, 2H), 7.69 (dd, J = 8.4, 1.3 Hz, 1H), 7.43 (d, J = 7.0 Hz, 2H), 7.39-7.30 (m, 4H), 7.30-7.26 (m, 1H), 7.22 (d, J = 7.4 Hz, 1H), 7.06 (dd, J = 4.1, 1.4 Hz, 1H), 6.88 (dd, J = 4.1, 2.7 Hz, 1H), 6.86-6.82 (m, 1H), 6.80 (dd, J = 7.6, 1.1 Hz, 1H), 4.45 (s, 2H), 2.44 (s, 3H); Carbon spectrum analysis: 13 C NMR(100MHz,Chloroform-d)δ:153.1,147.7,139.3,137.6,133.7,131.0,128.6,127.9,127. 2,126.8,126.7,126.2,125.5,120.3,115.5,114.7,113.9,111.7,111.4,109.5,47.9,18.1;

[0120] The structural formula of the pyrroloquinoxalinoquinazoline derivative of this embodiment is as follows:

[0121]

[0122] Embodiment 17

[0123] Under nitrogen protection, a mixture of 4-(4-bromophenyl)-7-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline (0.5mmol, 196mg), 6-phenyl-7,11b-dihydro-6-H pyrrolo[2',1':3,4]quinoxaline[1,2-c]quinazoline (0.6mmol, 1.2 equivalents) of the pyrroloquinoxaline and quinazoline derivative of Example 1, Cs2CO3 (325.8mg, 1.0mmol, 2.0 equivalents), Pd2(dba)3 (14mg, 0.015mmol, 0.03 equivalents), XPhos (28.6mg, 0.06mmol, 0.12 equivalents) and toluene (10mL) was added to a sealed tube. Then, the reaction mixture was heated to 100°C and stirred for 12 hours. Next, the reaction was quenched with brine, extracted with dichloromethane, and dried over anhydrous Na2SO4. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography (petroleum ether: dichloromethane = 2:1) to obtain 172 mg of a pale yellow product (yield 52%).

[0124] The NMR spectrum of the obtained compound is shown in the attached Fig.17 As shown, attached Fig.17 In the figure, A is the hydrogen spectrum and B is the carbon spectrum. Hydrogen spectrum analysis: 1 H NMR(400MHz,Chloroform-d)δ:8.35(d,J=2.0Hz,1H),8.08~8.01(m,3H),7.97(d,J=8.6Hz,1H),7.74( dd,J=8.5,2.1Hz,1H),7.66~7.59(m,2H),7.50~7.38(m,5H),7.37~7.28(m,2H),7.23(dd,J=3.0,1.5Hz ,1H),7.17(dd,J=4.1,1.2Hz,1H),7.06(td,J=7.9,1.7Hz,1H),7.01~6.97(m,2H),6.93~6.85(m,2H),6.80~6.68(m,2H),6.65(s,1H),6.39(t,J=3.2Hz,1H),6.18(dd,J=3.5,1.5Hz,1H),5.48(s,1H); Carbon spectrum analysis: 13CNMR (100 MHz, Chloroform-d) δ: 154.8, 148.9, 140.0, 139.5, 136.0, 135.0, 133.1 130.0, 129.2, 128.6, 127.9, 127.8, 127.7, 127.5, 125.4, 124.7, 123.7, 122.6, 122.6, 120.7, 119.8, 116.3, 115.6, 115.4, 115.2, 115.0, 114.4, 114.4, 110.1, 109.8, 108.0, 75.1, 50.7; HRMS-ESI (m / z) theoretical value C 42 H 28 F3N5[M+H] + :660.2353; measured value 660.2370; it can be seen that the structural formula of the compound is as follows:

[0125]

[0126] At the same time, its fluorescence performance was tested. Figure 18-19 As shown in the attached Figure 18-19 The data show that the maximum absorption wavelength of the pyrroloquinoxaline and quinazoline compound is 380 nm, the maximum fluorescence emission wavelength is 470 nm, the fluorescence lifetime is only 3.07 ns, x=0.187, y=0.313; the compound can emit bright blue light after being excited; indicating that the pyrroloquinoxaline and quinazoline derivatives provided by the present invention not only have excellent fluorescence properties, but also exhibit potential high-mobility electron transport properties, which make it have broad application prospects in organic electronic devices, such as organic light-emitting diodes (OLEDs), organic field effect transistors (OFETs) and other fields.

[0127] The remaining pyrroloquinoxaline and quinazoline derivatives of the present invention are also tested to have excellent fluorescence properties similar to those of the compound in Example 1, and have unique biological activities, can specifically bind to biomacromolecules such as enzymes, receptors, and DNA, thereby regulating biological processes such as cell signal transduction and gene expression, and can be used as drug skeletons.

[0128] The above contents are only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A class of pyrroloquinoxalinoquinazoline derivatives, It is characterized in that The structural formula of the pyrroloquinoxaline and quinazoline derivative is shown in Formula 1: Among them, R 1 Any one selected from a methyl group and a hydrogen atom; R 2 Any one selected from the group consisting of a hydrogen atom, a chlorine atom, a bromine atom, a trifluoromethyl group, a cyano group, a tert-butyl group, and a methyl group; R 3 Any one selected from a hydrogen atom, a chlorine atom, and a methyl group; R 4 Any one selected from the group consisting of a hydrogen atom, a methyl group, a nitro group, a chlorine atom, a bromine atom, a fluorine atom, a methyl group, a hydroxyl group, and a methoxy group, R 5 is selected from any one of a hydrogen atom and a bromine atom, X is selected from any one of carbon and nitrogen, Y is selected from any one of carbon and nitrogen, Z is selected from any one of carbon and nitrogen, and E is selected from any one of carbon, nitrogen and oxygen.

2. A pyrroloquinoxalinoquinazoline derivative according to claim 1, It is characterized in that The pyrroloquinoxalinoquinazoline derivatives have a structure as shown in Formula 2-17:

3. A method for synthesizing the pyrroloquinoxalinoquinazoline derivative according to any one of claims 1 to 2, It is characterized in that include: (1) preparing 2-(4,5-dihydropyrrolo[1,2-α]quinoxalin-4-yl)aniline compounds containing different substituents; The structural formula of the 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compound is as follows: Wherein R1 is selected from any one of a methyl group, a hydrogen atom, a chlorine atom, a bromine atom, a trifluoromethyl group, a cyano group, and a tert-butyl group; (2) dissolving the 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compound containing different substituents obtained in step (1) and an aromatic aldehyde compound in an organic solvent, adding an acidic catalyst in a mass percentage of 0.04% to 0.06%, cooling to room temperature and drying by spin drying, separating and purifying, and eluting to obtain a pyrroloquinoxaline and quinazoline derivative; The aromatic aldehyde compound is any one of benzaldehyde, o-bromobenzaldehyde, m-bromobenzaldehyde, p-bromobenzaldehyde, o-nitrobenzaldehyde, o-chlorobenzaldehyde, o-fluorobenzaldehyde, furanaldehyde and thiophenealdehyde.

4. The method for synthesizing the pyrroloquinoxalinoquinazoline derivative according to claim 3, It is characterized in that The acidic catalyst is any one of acetic acid, trifluoroacetic acid, hydrochloric acid, p-toluenesulfonic acid and methanesulfonic acid.

5. The method for synthesizing the pyrroloquinoxalinoquinazoline derivative according to claim 3, It is characterized in that The organic solvent is any one of dichloromethane, chloroform and dichloroethane.

6. The method for synthesizing the pyrroloquinoxalinoquinazoline derivative according to claim 3, It is characterized in that The molar ratio of the 2-(4,5-dihydropyrrolo[1,2-α]quinoxaline-4-yl)aniline compound containing different substituents to the aromatic aldehyde compound is 1-3:1-3.

7. The method for synthesizing the pyrroloquinoxalinoquinazoline derivative according to claim 3, It is characterized in that The reaction temperature is 20°C to 40°C, and the reaction time is 0.5h to 1h.

8. The method for synthesizing the pyrroloquinoxalinoquinazoline derivative according to claim 3, It is characterized in that The eluent used for separation and purification is a mixed solvent of petroleum ether and dichloromethane in a volume ratio of 2 to 15:1 or a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 2 to 15:

1.

9. Use of the pyrroloquinoxalinoquinazoline derivative according to any one of claims 1 to 2 in the preparation of organic semiconductor materials, It is characterized in that The pyrroloquinoxalinoquinazoline derivative is used as an organic semiconductor acceptor material.

10. Use of the pyrroloquinoxalinoquinazoline derivatives according to any one of claims 1 to 2 in the preparation of drug skeletons.

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