A dihydropyrroloquinazolinone compound containing trifluoromethyl and a synthesis method thereof

Abstract

The present invention proposes a dihydropyrroloquinazolinone compound containing trifluoromethyl and a synthesis method thereof, and belongs to the technical field of organic synthesis. The dihydropyrroloquinazolinone compound containing trifluoromethyl of the present invention is prepared by a free radical tandem cyclization reaction of CF3Br and N-cyano-N-alkenylamide in an organic solvent under visible light induction and the presence of a photocatalyst and a base. The present invention is the first to regulate the regioselectivity of the substrate under photocatalysis, directly introduce the trifluoromethyl group into the dihydropyrroloquinazolinone ring, and obtain a trifluoromethyl-substituted dihydropyrroloquinazolinone, which can be further used to prepare drugs with anti-Alzheimer's disease. The present invention provides a new method for the synthesis of functionalized dihydropyrroloquinazolinone compounds, which has the advantages of cheap and readily available raw materials, short reaction steps, high regioselectivity of the reaction, simple operation, mild reaction conditions, and good reaction yield.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a dihydropyrroloquinazolinone compound containing a trifluoromethyl group and a synthesis method thereof. Background Art

[0002] Quinazolinone is an important class of heterocyclic compounds, and its structural units are often found in some natural products, drugs and bioactive molecules. Compared with the widely studied quinazolinone, dihydropyrroloquinazolinone is a unique nitrogen-fused alkaloid, which has attracted the attention of many organic chemists and biologists in recent years due to its good biological activity and potential therapeutic ability. For example, compounds with the following A-G chemical structures:

[0003]

[0004] Studies have shown that compound A, deoxyvasicinone, is an alkaloid compound isolated from plants and has antidepressant activity (Nat. Prod. Rep., 2007, 24, 223); compound B, vasisinone, is a quinazolinone alkaloid isolated from Artemisia selengensis and has anti-inflammatory activity (Beilstein J. Org. Chem., 2015, 11, 416); compound C, Luotonin A, is a quinazolinone alkaloid isolated from Artemisia camelium and is an antiviral and anti-phytopathogenic fungal agent with good antiviral activity against tobacco mosaic virus and also has certain inhibitory activity against topoisomerase I and topoisomerase II (Heterocycles, 1997, 46, 541); compound D, phaitanthrins Compound A has anticancer activity (J.Nat.Prod.2008,71,1275); Compound E, Tryptanthrin has anti-infective activity (Nat.Prod.Rep.2004,21,650); Compound F has anti-Alzheimer's disease activity (Tetrahedron,2006,62,9787); Compound G, Isaindigotone can be used as a superoxide scavenger and participate in human metabolic processes (J.Nat.Prod.,2001,64,1297). Therefore, in order to further expand the new method of synthesizing the skeleton and explore the potential application value of quinazolinone derivatives, it will be very necessary to synthesize various condensed-ring quinazolinone derivatives.

[0005] In the past few decades, free radical tandem cyclization strategies have been shown to rapidly obtain important heterocyclic skeletons from traditional raw materials. Moreover, in free radical tandem cyclization reactions, the use of nitriles as starting materials has the characteristics of high efficiency and mild reaction conditions, and is an important way to construct complex and useful nitrogen-containing skeletons. According to literature research, N-cyano-N-enylamides have been shown to be an effective synthetic building block for the synthesis of quinazolinone compounds by constructing quinazolinone skeletons through a key imine radical intermediate in free radical tandem cyclization reactions.

[0006] At present, the synthesis of dihydropyrroloquinazolinone compounds using free radical tandem cyclization strategies is mainly achieved by using unactivated olefins such as N-cyano-N-alkenylamide substrates for self-radical tandem cyclization, or N-cyano-N-alkenylamide and other free radicals for free radical tandem cyclization. The specific methods are as follows:

[0007] (1) Self-radical cascade cyclization of N-cyano-N-enylamide substrates

[0008] This is the earliest traditional method for synthesizing dihydropyrroloquinazolinone compounds by using the free radical tandem cyclization strategy of N-cyano-N-alkenylamide. In this reaction, under the action of tributyltin hydride reagent and free radical initiator (AIBN) azobisisobutyronitrile, the aromatic radical generated in situ by N-(2-iodobenzyl)-N-cyanoamide attacks the cyano carbon to generate a stable imine carbon radical, and then an intramolecular free radical tandem cyclization reaction occurs to synthesize dihydropyrroloquinazolinone compounds. The reaction formula is:

[0009]

[0010] This free radical tandem cyclization reaction was first reported by Max Malacria et al. in 2007. The advantage of this method is that it realizes the total synthesis of Luotonin A alkaloids (reference: Angew.Chem.Int.Ed.2007,46,576-579). However, the biggest problem of this method is the use of toxic reagent tributyltin hydride. Subsequently in 2010, the research group designed a new N-cyano-N-alkenylamide substrate, and also obtained dihydropyrroloquinazolinone compounds through free radical tandem cyclization (J.Am.Chem.Soc.2010,132,4381-4387). However, the toxic reagent tributyltin hydride is still used, the reaction conditions are harsh, and it needs to be carried out at high temperature, and the scope of application of the substrate is limited, which further limits the use of this method.

[0011] In 2016, Yu Shouyun's research group proposed the use of photocatalytic redox strategy (J.Org.Chem.2016,81,7276-7281), starting from N-(2-iodobenzyl)-N-cyanamide, with the assistance of photocatalyst and base DIPEA, acetonitrile as solvent, to synthesize dihydropyrroloquinazolinone derivatives at room temperature. This method avoids the use of toxic reagent tributyltin hydride and conforms to the concept of green chemical synthesis. The reaction formula is:

[0012]

[0013] In 2020, Turner's group reported a free radical tandem cyclization reaction of N-cyano-N-enylamide mediated by hydrogen atom transfer (HAT) (Chem. Eur. J. 2020, 26, 3026-3029). This method uses phenylsilane and triacetylacetonate iron as catalytic agents, isopropanol as solvent, and reacts at 50°C for 1-3 hours to obtain spirodihydropyrroloquinazolinone derivatives. The advantages of this method are short reaction time and the generation of free radicals through a new method (HAT) strategy. The reaction formula is:

[0014]

[0015] (2) Tandem cyclization reaction of N-cyano-N-enylamide substrates with other free radicals

[0016] In 2016, Cui Sunliang's research group proposed a silver (I)-mediated free radical tandem cyclization reaction of N-cyano-N-alkenyl amides to obtain phosphorylated dihydropyrroloquinazolinone derivatives (Org. Lett. 2016, 18, 1768-1771). The advantage of this method is that the substrate has a wide range of applicability, and the introduction of phosphoryl groups into the dihydropyrroloquinazolinone skeleton enables the construction of complex molecules. In the same year, the research group developed a method for introducing trifluoromethyl groups into the molecule using Togni reagents to obtain trifluoroethyl-substituted dihydropyrroloquinazolinone compounds (Adv. Synth. Catal. 2016, 358, 746-751). The advantage of this method is that for the first time, trifluoromethyl reagents are used to achieve trifluoroethylation of unactivated olefins, including terminal olefins and internal olefins. The disadvantage is that transition metal catalysis is used, and the Togni reagent used is expensive, cumbersome to prepare, and difficult to store. The reaction formula is:

[0017]

[0018] In 2017, Pan Yi's research group developed a metal-free free radical tandem cyclization / decarbonylation reaction of N-cyano-N-alkenylamides with various secondary aldehydes or tertiary alkyl aldehydes under the action of DTBP (di-tert-butyl peroxide), and constructed dihydropyrroloquinazolinone derivatives (Org. Chem. Front., 2017, 4, 2370-2374). The disadvantage of this method is that the scope of application of substrates is limited, that is, aldehydes are limited to secondary or tertiary fatty aldehydes. The reaction formula is:

[0019]

[0020] In the same year, the research group also disclosed a highly efficient photocatalytic oxidation / reduction cyclization reaction of N-cyano-N-alkenylamide with aryl sulfonic acid or aryl sulfonyl chloride (Org. Lett. 2017, 19, 4798-4801), which effectively constructed the CS bond. The advantages of this reaction are: it has easily available sulfonation reagents and is carried out under mild conditions, providing a new strategy for the synthesis of sulfonated dihydropyrroloquinazolinone drugs. The reaction formula is:

[0021]

[0022] In 2018, Cui Sunliang's research group disclosed a silver-catalyzed free radical tandem cyclization reaction of N-cyano-N-enylamides and 1,3-dicarbonyl compounds such as ethyl acetoacetate (Org. Biomol. Chem., 2018, 16, 5899-5906). Dihydropyrroloquinazolinone compounds were synthesized by a simple method. The method has mild reaction conditions, the raw materials are easily available, and the obtained products can be further derivatized to synthesize oxazole and pyrazole derivatives. The reaction formula is:

[0023]

[0024] In 2020, Wang Qingming's research group disclosed a radical tandem cyclization reaction of N-cyano-N-alkenylamide and trifluoromethanethiol silver (Org. Biomol. Chem., 2020, 18, 1994-2001), thereby introducing a trifluoromethylthio group to the dihydropyrroloquinazolinone ring and synthesizing a series of dihydroindolequinazolinone derivatives. The characteristics of this reaction are: the substrate is synthesized and put into the reaction for the first time, and it is also the first reaction to introduce the SCF3 group into this type of reaction. The reaction formula is:

[0025]

[0026] In 2022, Xu Pengfei's research group disclosed a visible light-catalyzed free radical tandem cyclization reaction of N-cyano-N-alkenylamide and trifluoroacetic anhydride (J.Org.Chem.2022,87,1493-1501), and synthesized a series of trifluoroethyl-substituted dihydropyrroloquinazolinone derivatives. The characteristics of this reaction are: only light is required, no photocatalyst is required, which is superior to traditional methods that require high temperature, oxidants, metal catalysts and external photocatalysts. It is more environmentally friendly and has certain synthetic significance. It should be noted that the structure of this compound is similar to the structure of compound F that can treat Alzheimer's disease. The reaction formula is:

[0027]

[0028] In 2024, Yang Wenchao's research group disclosed a visible light-induced free radical tandem difluoroalkylation / cyclization reaction of N-cyano-N-alkenylamide and ethyl bromodifluoroacetate (Org. Lett. 2024, 26, 2119-2123). Using the cheap non-metal 4CzIPN as a photocatalyst, a variety of difluoroethyl-containing dihydropyrroloquinazolinone compounds were obtained, which are very similar to the structure of compound F that can treat Alzheimer's disease. The characteristics of this reaction are that it provides a new method for obtaining valuable condensed-ring quinazolinones quickly, simply and practically, and can achieve gram-scale reactions. The reaction formula is:

[0029]

[0030] In summary, various dihydropyrroloquinazolinone derivatives have been synthesized from N-cyano-N-alkenylamides through free radical tandem cyclization strategies, but each method has its own defects and limitations. Trifluoromethyl is a common fluorinated group. The introduction of trifluoromethyl into organic compounds can significantly change the chemical, physical and biological properties of the parent compound, such as acidity, bioavailability, metabolic stability, lipid solubility and protein binding ability. The results of literature survey show that there is no report on the synthetic method of directly introducing trifluoromethyl into the dihydropyrroloquinazolinone ring. In order to further explore the synthetic method of compounds and their analogues for the treatment of Alzheimer's disease and improve and enhance the biological activity of quinazolinone compounds, it is very necessary to explore a new, efficient and simple synthetic method to prepare dihydropyrroloquinazolinone compounds containing trifluoromethyl. Summary of the invention

[0031] To solve the above technical problems, the present invention proposes a trifluoromethyl-containing dihydropyrroloquinazolinone compound and a synthesis method thereof, using N-cyano-N-alkenylamide as a raw material, and trifluorobromomethane (CF3Br) which is cheap and readily available as a fluorination agent, and under the induction of visible light and the action of a photocatalyst and a base, a free radical tandem cyclization reaction is performed to prepare a trifluoromethyl-containing dihydropyrroloquinazolinone derivative in one step. The present invention directly introduces a trifluoromethyl group into the dihydropyrroloquinazolinone ring for the first time, and the obtained dihydropyrroloquinazolinone can be further used to prepare a drug having the effect of treating Alzheimer's disease. The method is green and safe, with cheap and readily available raw materials, high atom economy, good regioselectivity of the reaction, mild reaction conditions, a wide range of substrate applications, and easy purification of the product, and belongs to green synthesis.

[0032] To achieve the above object, the present invention provides a dihydropyrroloquinazolinone compound containing a trifluoromethyl group, the general structural formula of which is:

[0033]

[0034] Wherein, R is H, 4-Me, 4- t Any one of Bu, 4-CF3, 4-NO2.

[0035] The present invention also provides a method for preparing the dihydropyrroloquinazolinone compound containing a trifluoromethyl group, wherein the dihydropyrroloquinazolinone compound containing a trifluoromethyl group is prepared by a free radical tandem cyclization reaction of CF3Br and N-cyano-N-alkenylamide in an organic solvent under the induction of visible light and in the presence of a photocatalyst and a base.

[0036] Furthermore, the structural formula of the N-cyano-N-alkenyl amide is:

[0037]

[0038] Wherein, R is H, 4-Me, 4- t Any one of Bu, 4-CF3, 4-NO2.

[0039] Furthermore, the CF3Br is CF3Br gas, and the pressure of the introduced CF3Br gas is 1.0 atm.

[0040] Further, the base includes any one of K2CO3, Na2CO3, Cs2CO3, Li2CO3, KOH, K3PO4 and TMEDA (N,N,N',N'-tetramethylethylenediamine), preferably K2CO3.

[0041] Furthermore, the molar ratio of the N-cyano-N-alkenylamide to the base is 1:(1-2.5), preferably 1:1.5.

[0042] Furthermore, the photocatalyst (PC) is one of a noble metal catalyst or an organic dye catalyst, and the amount of the photocatalyst used is 0.5 mol% to 2.0 mol%, preferably 1.5 mol%, of the amount of the N-cyano-N-alkenylamide used.

[0043] Furthermore, the noble metal catalyst is fac-Ir III (ppy) 3, the organic dye catalyst is 4CzIPN (2,4,5,6-tetrakis (9-carbazolyl) -isophthalonitrile) or 3DPA2FBN (2,4,6-tris (diphenylamino) -3,5-difluorobenzonitrile), preferably fac-Ir III (ppy)3.

[0044] Furthermore, the visible light is blue light with a wavelength of 390nm to 460nm and a power of 5W to 20W, preferably 10W blue light.

[0045] Furthermore, the organic solvent includes any one of DCM, CH3CN, NMP, DMSO, THF, acetone and 1,4-dioxane, preferably CH3CN.

[0046] Furthermore, the reaction time is 12 to 48 hours, and the reaction temperature is room temperature.

[0047] Furthermore, the preparation method of the trifluoromethyl-containing dihydropyrroloquinazolinone compound comprises the following specific steps:

[0048] N-cyano-N-alkenylamide 1 (1-3 equiv.), PC (0.5 mol%-2.0 mol%, representing the molar percentage of PC in N-cyano-N-alkenylamide), base (2-6 equiv.), and 1-5 mL of organic solvent are added to a 50 mL Schlenk flask. The Schlenk flask is evacuated and then filled with CF3Br gas, and the process is repeated three to six times. Finally, the pressure in the Schlenk flask is maintained at 1.0 atm-1.5 atm (observed from a barometer). The reaction mixture is placed on a blue light source with a wavelength of 390 nm-460 nm and a power of 5 W-20 W, and stirred at room temperature for 12-48 h. After the reaction is completed, the solvent is dried by spin drying, and column chromatography is performed with silica gel as the stationary phase and petroleum ether and ethyl acetate as the eluent (PE:EA=(6-15):1, volume ratio) to obtain the dihydropyrroloquinazolinone compound containing trifluoromethyl. The reaction equation is:

[0049]

[0050] The present invention also proposes the use of the dihydropyrroloquinazolinone compound containing a trifluoromethyl group in the preparation of a drug having an anti-Alzheimer's disease effect.

[0051] Compared with the prior art, the present invention has the following advantages and technical effects:

[0052] (1) The present invention is the first to use a free radical tandem cyclization reaction involving N-cyano-N-alkenylamide to synthesize dihydropyrroloquinazolinone compounds. This method directly introduces a trifluoromethyl group into the dihydropyrroloquinazolinone compound while constructing the ring, providing a new raw material for the synthesis of dihydropyrroloquinazolinone compounds with trifluoromethyl substitution.

[0053] (2) The present invention is the first to use trifluorobromomethane for a free radical tandem cyclization reaction involving N-cyano-N-enylamide to construct a trifluoromethyl-substituted dihydropyrroloquinazolinone compound. CF3Br is a non-toxic, odorless, cheap and readily available industrial raw material. Compared with other fluorination agents, its greatest advantages are low price, easy availability and high atom economy.

[0054] (3) The trifluoromethyl-substituted dihydropyrroloquinazolinone synthesized in the present invention can be further used to prepare drugs with anti-Alzheimer's disease effects.

[0055] (4) The synthesis method provided by the present invention has a high regioselectivity, that is, all obtained are 3,3-dimethyl-2-trifluoromethyl dihydropyrroloquinazolinone compounds. The synthesis method has the characteristics of short reaction steps, high atom utilization, simple operation, mild reaction conditions and high reaction yield, and uses visible light irradiation to generate free radicals, thereby achieving green synthesis.

[0056] (5) The dihydropyrroloquinazolinone compound synthesized by the present invention is 1 H NMR, 13 C NMR, 19 F NMR high-resolution mass spectrometry detection, the product is a pure target compound with high product purity. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] The drawings constituting a part of the present application are used to provide a further understanding of the present application. The illustrative embodiments and descriptions of the present application are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0058] Figure 1 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 1 1 H NMR spectra;

[0059] Figure 2 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 1 13 C NMR spectra;

[0060] Figure 3 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 1 19 F NMR spectra;

[0061] Figure 4 This is a high-resolution mass spectrum monitoring diagram of 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 1;

[0062] Figure 5 3,3,6-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 2 1 H NMR spectra;

[0063] Figure 6 3,3,6-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 2 13 C NMR spectra;

[0064] Figure 7 3,3,6-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 2 19 F NMR spectra;

[0065] Figure 8 This is a high-resolution mass spectrometry monitoring diagram of 3,3,6-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 2;

[0066] Fig. 9 The 6-(tert-butyl)-3,3-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 3 1 H NMR spectra;

[0067] Fig.10 The 6-(tert-butyl)-3,3-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 3 13C NMR spectra;

[0068] Fig.11 The 6-(tert-butyl)-3,3-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 3 19 F NMR spectra;

[0069] Fig.12 This is a high-resolution mass spectrum monitoring diagram of 6-(tert-butyl)3,3-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 3;

[0070] Fig.13 3,3-dimethyl-2,6-bis(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 4 1 H NMR spectra;

[0071] Fig.14 3,3-dimethyl-2,6-bis(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 4 13 C NMR spectra;

[0072] Fig.15 3,3-dimethyl-2,6-bis(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 4 19 F NMR spectra;

[0073] Fig.16 This is a high-resolution mass spectrum monitoring diagram of 3,3-dimethyl-2,6-bis(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 4;

[0074] Fig.17 3,3-dimethyl-6-nitro-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 5 1 H NMR spectra;

[0075] Fig.18 3,3-dimethyl-6-nitro-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 5 13 C NMR spectra;

[0076] Fig.193,3-dimethyl-6-nitro-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 5 19 F NMR spectra;

[0077] Fig. 20 This is a high-resolution mass spectrum monitoring chart of 3,3-dimethyl-6-nitro-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one synthesized in Example 5. DETAILED DESCRIPTION

[0078] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0079] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0080] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0081] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0082] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0083] The embodiment of the present invention provides a dihydropyrroloquinazolinone compound containing a trifluoromethyl group, and the general structural formula thereof is:

[0084]

[0085] Wherein, R is H, 4-Me, 4- t Any one of Bu, 4-CF3, 4-NO2.

[0086] The embodiment of the present invention also provides a method for preparing the dihydropyrroloquinazolinone compound containing trifluoromethyl, wherein CF3Br and N-cyano-N-alkenylamide undergo a free radical tandem cyclization reaction in an organic solvent under the induction of visible light and in the presence of a photocatalyst and a base to prepare a trifluoromethyl-substituted dihydropyrroloquinazolinone compound.

[0087] In a preferred embodiment of the present invention, the structural formula of the N-cyano-N-alkenyl amide is:

[0088]

[0089] Wherein, R is H, 4-Me, 4- t Any one of Bu, 4-CF3, 4-NO2.

[0090] In a preferred embodiment of the present invention, the CF3Br introduced is CF3Br gas, which is maintained at 1.0 atm.

[0091] In a preferred embodiment of the present invention, the base includes any one of K2CO3, Na2CO3, Cs2CO3, Li2CO3, KOH, K3PO4 and TMEDA (N,N,N',N'-tetramethylethylenediamine), more preferably K2CO3.

[0092] In a preferred embodiment of the present invention, the molar ratio of the N-cyano-N-alkenylamide to the base is 1:(1-2.5), preferably 1:1.5.

[0093] In a preferred embodiment of the present invention, the photocatalyst (PC) is a noble metal catalyst or an organic dye catalyst, and the amount of the photocatalyst is 0.5 mol% to 2.0 mol%, preferably 1.5 mol%, of the amount of the N-cyano-N-alkenylamide.

[0094] In a preferred embodiment of the present invention, the noble metal catalyst is fac-Ir III (ppy) 3, the organic dye catalyst is 4CzIPN (2,4,5,6-tetrakis (9-carbazolyl) -isophthalonitrile) or 3DPA2FBN (2,4,6-tris (diphenylamino) -3,5-difluorobenzonitrile), preferably fac-Ir III (ppy)3.

[0095] In a preferred embodiment of the present invention, the visible light is blue light with a wavelength of 390nm to 460nm and a power of 5W to 20W, preferably 10W blue light.

[0096] In a preferred embodiment of the present invention, the organic solvent includes any one of DCM, CH3CN, NMP, DMSO, THF, acetone and 1,4-dioxane, preferably CH3CN.

[0097] In a preferred embodiment of the present invention, the reaction time is 12 to 48 hours, and the reaction temperature is room temperature.

[0098] All raw materials used in the examples of the present invention were purchased from commercial sources. Among them, the raw material N-cyano-N-alkenylamide used in the following examples was prepared according to the literature (Org. Lett. 2022, 24, 1110.).

[0099] The room temperature in the embodiments of the present invention refers to "25±3°C".

[0100] The technical solution of the present invention is further illustrated by the following embodiments.

[0101] Example 1

[0102] Synthesis of 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a)

[0103] The synthetic route is as follows:

[0104]

[0105] The specific synthesis process is as follows:

[0106] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 44.0 mg, yield 78%.

[0107] The 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a) synthesized above was 1 HNMR, 13 CNMR, 19 FNMR high-resolution mass spectrometry detection (such as Figure 1-4 As shown), it can be concluded that the product is a pure target compound. The characterization data of the corresponding product are:

[0108] 1 H NMR (400MHz, CDCl3) δ8.29(d,J=8.0,1H),7.77-7.69(m,2H),7.49-7.45(m,1H),4.44(dd,J= 12.8,8.4Hz,1H),4.17(dd,J=12.8,8.4Hz,1H),3.05-2.94(m,1H),1.60(s,3H),1.48(s,3H).

[0109] 13 C{ 1 H}NMR(150MHz,CDCl3)162.4,160.4,149.2,134.3,125.9(q,J C-F =277.8Hz),127.3,126.6,126.4,120.7,48.3(q,J C-F =27.5Hz),44.8,43.0(q,J C-F =3.6Hz),26.6,21.5.

[0110] 19 F NMR (376MHz, CDCl3) δ, -65.58, (d, J = 9.02Hz);

[0111] HRMS(ESI):m / z calcd for C 14 H 14 ON2F3[M+H] + 283.1053, found 283.1052.

[0112] Example 2

[0113] Synthesis of 3,3,6-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3b)

[0114] The synthetic route is as follows:

[0115]

[0116] The specific synthesis process is as follows:

[0117] N-cyano-4-methyl-N-(3-methylbut-2-en-1-yl)benzamide (45.7 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=7:1) to obtain 3,3,6-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3b): white solid, 37.9 mg, yield 64%.

[0118] The 3,3,6-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3b) synthesized above was 1 HNMR, 13 C NMR, 19 F NMR high-resolution mass spectrometry detection (such as Figure 5-8 The results show that the product is a pure target compound. The characterization data of the corresponding product are:

[0119] 1 H NMR (400MHz, CDCl3) δ8.16(d,J=8.4Hz,1H),7.51(s,1H),7.28(d,J=8.0Hz,1H),4.42(dd,J=12.4,8 .4Hz,1H),4.13(dd,J=12.8,8.4Hz,1H),3.04-2.93(m,1H),2.49(s,3H),1.59(s,3H),1.47(s,3H);

[0120] 13 C{ 1 H}NMR(150MHz,CDCl3)δ162.5,160.4,149.4,145.4,127.9(q,J C-F =291.2Hz),128.1,127.1,126.2,118.3,48.3(q,J C-F=27.5Hz),44.7,42.9(q,J C-F =3.5Hz),26.5,21.8,21.5;

[0121] 19 F NMR (376MHz, CDCl3) δ-65.58, (d, J=8.65Hz);

[0122] HRMS(ESI):m / z calcd for C 15 H 16 ON2F3[M+H] + 297.1209, found 297.1207.

[0123] Example 3

[0124] The synthesis route of 6-(tert-butyl)3,3-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3c) is as follows:

[0125]

[0126] The specific synthesis process is as follows:

[0127] 4-tert-Butyl-N-cyano-4-methyl-N-(3-methylbut-2-en-1-yl)benzamide (54.1 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=8:1) to obtain 6-(tert-butyl)3,3-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3c): white solid, 41.3 mg, yield 61%.

[0128] The 6-(tert-butyl)3,3-trimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3c) synthesized above was 1 H NMR, 13 C NMR, 19 F NMR high-resolution mass spectrometry detection (such as Figure 9-12 The results show that the product is a pure target compound. The characterization data of the corresponding product are:

[0129] 1 H NMR (400MHz, CDCl3) δ8.20(d,J=8.4Hz,1H),7.70(s,1H),7.53(d,J=8.4Hz,1H),4.42(dd,J=12.8,8 .4Hz,1H),4.14(dd,J=12.4,8.0Hz,1H),3.03-2.92(m,1H),1.60(s,3H),1.48(s,3H),1.39(s,3H);

[0130] 13 C{ 1 H}NMR(150MHz,CDCl3)δ162.4,160.3,158.5,149.3,125.9(q,J C-F =276.6Hz),126.0,124.7,123.5,118.2,48.3(q,J C-F =28.2Hz),44.7,42.9(q,J C-F =5.0Hz),35.3,31.0,26.6,21.5;

[0131] 19 F NMR (376MHz, CDCl3) δ-65.59, (d, J=9.40Hz);

[0132] HRMS(ESI):m / z calcd for C 18 H 22 ON2F3[M+H] + 339.1679, found 339.1679.

[0133] Example 4

[0134] Synthesis of 3,3-dimethyl-2,6-bis(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3d)

[0135] The synthetic route is as follows:

[0136]

[0137] The specific synthesis process is as follows:

[0138] N-cyano-4-methyl-N-(3-methylbut-2-en-1-yl)-4-(trifluoromethyl)benzamide (56.5 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=8:1) to obtain 3,3-dimethyl-2,6-bis(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3d): white solid, 52.5 mg, yield 75%.

[0139] The 3,3-dimethyl-2,6-bis(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3d) synthesized above was 1 HNMR, 13 C NMR, 19 F NMR, high-resolution mass spectrometry (such as Figure 13-16 The results show that the product is a pure target compound. The characterization data of the corresponding product are:

[0140] 1 H NMR (400MHz, CDCl3) δ8.38 (d, J=8.4Hz, 1H), 8.00 (s, 1H), 7.66 (d, J=8.8Hz, 1H), 4.45 (dd, J= 13.2,8.4Hz,1H),4.18(dd,J=13.2,8.4Hz,1H),3.07-2.96(m,1H),1.60(s,3H),1.49(s,3H);

[0141] 13 C{ 1 H}NMR(150MHz,CDCl3)δ163.9,159.6,149.3,135.9(q,J C-F =32.6Hz),127.6(q,J C-F =277.4Hz),127.5,124.9(q,J C-F =4.1Hz),123.3(q,J C-F =271.8Hz),123.1,122.6(q,J C-F=3.5Hz),48.2(q,J C-F =27.8Hz),45.0,43.2(q,J C-F =3.8Hz),26.6,21.4;

[0142] 19 F NMR(376MHz, CDCl3)δ-63.27(s),-65.69,(d,J=9.02Hz);

[0143] HRMS(ESI):m / z calcd for C 15 H 13 ON2F6[M+H] + 351.0927, found 351.0925.

[0144] Example 5

[0145] Synthesis of 3,3-dimethyl-6-nitro-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3e)

[0146] The synthetic route is as follows:

[0147]

[0148] The specific synthesis process is as follows:

[0149] N-cyano-N-(3-methylbut-2-en-1-yl)-4-nitrobenzamide (51.9 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, and this process was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=12:1) to obtain 3,3-dimethyl-6-nitro-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3e): white solid, 38.0 mg, yield 58%.

[0150] The synthesized 3,3-dimethyl-6-nitro-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3e) was 1 H NMR,13 C NMR, 19 F NMR (such as Figure 17-20 The results show that the product is a pure target compound. The characterization data of the corresponding product are:

[0151] 1 H NMR (400MHz, CDCl3) δ8.55(d,J=2.0Hz,1H),8.44(d,J=8.8Hz,1H),8.22(dd,J=8.8,2.0Hz,1H),4.46 (dd,J=12.8,8.4Hz,1H),4.20(dd,J=12.8,8.0Hz,1H),3.09-2.98(m,1H),1.62(s,3H),1.51(s,3H);

[0152] 13 C{ 1 H}NMR(150MHz,CDCl3)δ164.8,159.1,151.5,149.9,125.7(q,J C-F =277.5Hz),128.2,124.9,123.0,120.2,48.2(q,J C-F =27.8Hz),45.1,43.3(q,J C-F =3.6Hz),26.6,21.4;

[0153] 19 F NMR (376MHz, CDCl3) δ-65.69, (d, J=9.02Hz);

[0154] HRMS(ESI):m / z calcd for C 14 H 13 O3N3F3[M+H] + 328.0904, found 328.0903.

[0155] Example 6

[0156] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Cs2CO3 (130.3 mg, 0.4 mmol, 2.0 equiv), and 3 mL of 1,4-dioxane were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, and the process was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 22.0 mg, yield 39%.

[0157] Example 7

[0158] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Cs2CO3 (130.3 mg, 0.4 mmol, 2.0 equiv), and 3 mL of THF were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 20.9 mg, yield 37%.

[0159] Example 8

[0160] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Cs2CO3 (130.3 mg, 0.4 mmol, 2.0 equiv), and 3 mL of DCM were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 24.3 mg, yield 43%.

[0161] Example 9

[0162] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Cs2CO3 (130.3 mg, 0.4 mmol, 2.0 equiv), and 3 mL of acetone were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, and this process was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 27.1 mg, yield 48%.

[0163] Example 10

[0164] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Cs2CO3 (130.3 mg, 0.4 mmol, 2.0 equiv), and 3 mL of NMP were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 10.1 mg, yield 18%.

[0165] Embodiment 11

[0166] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Cs2CO3 (130.3 mg, 0.4 mmol, 2.0 equiv), and 3 mL of DMSO were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, and this process was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 19.2 mg, yield 34%.

[0167] Example 12

[0168] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Li2CO3 (29.6 mg, 0.4 mmol, 2.0 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, and this process was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 33.9 mg, yield 60%.

[0169] Embodiment 13

[0170] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), Na2CO3 (42.4 mg, 0.4 mmol, 2.0 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 27.7 mg, yield 49%.

[0171] Embodiment 14

[0172] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), KOH (22.4 mg, 0.4 mmol, 2.0 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 19.8 mg, yield 35%.

[0173] Embodiment 15

[0174] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), K3PO4 (84.9 mg, 0.4 mmol, 2.0 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 29.9 mg, yield 53%.

[0175] Example 16

[0176] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), K2CO3 (27.6 mg, 0.2 mmol, 1.0 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 35.6 mg, yield 63%.

[0177] Embodiment 17

[0178] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.31 mg, 1 mol%), K2CO3 (69.1 mg, 0.5 mmol, 2.5 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 27.1 mg, yield 48%.

[0179] Embodiment 18

[0180] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (0.65 mg, 0.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 18.6 mg, yield 33%.

[0181] Embodiment 19

[0182] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (2.62 mg, 2.0 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, and this process was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 37.9 mg, yield 67%.

[0183] Embodiment 20

[0184] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 14.7 mg, yield 26%.

[0185] Embodiment 21

[0186] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), 3DPA2FBN (1.92 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 19.2 mg, yield 34%.

[0187] Embodiment 22

[0188] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 5 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 37.9 mg, yield 67%.

[0189] Embodiment 23

[0190] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 15 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 26.0 mg, yield 46%.

[0191] Embodiment 24

[0192] N-cyano-N-(3-methylbut-2-en-1-yl)benzamide (43 mg, 0.2 mmol, 1.0 equiv), fac-Ir(ppy)3 (1.96 mg, 1.5 mol%), K2CO3 (41.5 mg, 0.3 mmol, 1.5 equiv), and 3 mL CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF3Br gas, which was repeated three times. Finally, the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 20 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=6:1, volume ratio, the same below) to obtain 3,3-dimethyl-2-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (3a): white solid, 29.9 mg, yield 53%.

[0193] Related applications

[0194] The literature Tetrahedron, 2006, 62, 9787 reported compound F (structural formula ) has the potential to treat Alzheimer's disease. The present invention provides a new method for synthesizing a trifluoromethyl-substituted dihydropyrroloquinazolinone compound, thereby illustrating that the compounds prepared in the embodiments of the present invention can be used to prepare drugs for treating Alzheimer's disease.

[0195] The above are only preferred specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A dihydropyrroloquinazolinone compound containing a trifluoromethyl group, characterized in that: Its general structural formula is: Wherein, R is H, 4-Me, 4- t Any one of Bu, 4-CF3, 4-NO2.

2. A method for preparing a dihydropyrroloquinazolinone compound containing a trifluoromethyl group according to claim 1, characterized in that: Under the induction of visible light and in the presence of a photocatalyst and a base, a free radical tandem cyclization reaction occurs between CF3Br and N-cyano-N-alkenylamide in an organic solvent to prepare the dihydropyrroloquinazolinone compound containing a trifluoromethyl group.

3. The method for preparing a dihydropyrroloquinazolinone compound containing a trifluoromethyl group according to claim 2, characterized in that: The CF3Br is CF3Br gas, and the pressure of the introduced CF3Br gas is 1.0 atm.

4. The method for preparing a dihydropyrroloquinazolinone compound containing a trifluoromethyl group according to claim 2, characterized in that: The base includes any one of K2CO3, Na2CO3, Cs2CO3, Li2CO3, KOH, K3PO4 and TMEDA; The organic solvent includes any one of DCM, CH3CN, NMP, DMSO, THF, acetone and 1,4-dioxane.

5. The method for preparing a dihydropyrroloquinazolinone compound containing a trifluoromethyl group according to claim 2, characterized in that: The molar ratio of the N-cyano-N-alkenylamide to the base is 1:(1-2.5).

6. The method for preparing a dihydropyrroloquinazolinone compound containing a trifluoromethyl group according to claim 2, characterized in that: The photocatalyst is one of a noble metal catalyst and an organic dye catalyst, and the amount of the photocatalyst used is 0.5 mol% to 2.0 mol% of the amount of the N-cyano-N-alkenylamide used.

7. The method for preparing a dihydropyrroloquinazolinone compound containing a trifluoromethyl group according to claim 6, characterized in that: The noble metal catalyst is fac-Ir III (ppy)3, the organic dye catalyst is 4CzIPN or 3DPA2FBN.

8. The method for preparing a dihydropyrroloquinazolinone compound containing a trifluoromethyl group according to claim 2, characterized in that: The visible light is blue light with a wavelength of 390nm to 460nm and a power of 5W to 20W.

9. The method for preparing a trifluoromethyl-containing dihydropyrroloquinazolinone compound according to claim 2, characterized in that: The reaction time is 12 to 48 hours, and the reaction temperature is room temperature.

10. Use of the dihydropyrroloquinazolinone compound containing a trifluoromethyl group as claimed in claim 1 in the preparation of a drug having an anti-Alzheimer's disease effect.

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