A process for the synthesis of 5,6-dihydroimidazo[1,2-c]quinazolines and derivatives thereof

Abstract

The application relates to a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and derivatives thereof, which comprises the following steps: reacting boric acid or boric ester with (trimethylsilyl)ethoxymethyl-protected imidazole halide, and then ring-closing under acidic conditions to obtain the target product. The application provides a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and derivatives thereof, and the method has the advantages of simple synthesis operation, mild reaction condition, improved synthesis efficiency and reduced synthesis cost.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, and particularly relates to a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and derivatives thereof. BACKGROUND

[0002] More and more evidence shows that in many diseases, the increase of oxygen free radical level and the acceleration of lipid peroxidation can cause structural damage and functional impairment of cell membranes, and eventually lead to cell death. Based on the design concept of protecting different tissues at risk of oxidative stress, lipid peroxidation inhibition is considered to be a biological property of many drugs. 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives are widely concerned as a new antioxidant building block, that is, easy to oxidize or capable of reducing free radicals, while suitable for incorporation into molecules with other valuable pharmacological activities.

[0003] The reaction equation of the synthesis process in the prior art is shown in Figures 1-5 The existing synthesis route is long, the operation is complicated, and the type / quantity of the derivative product is limited due to the problem of derivation of the raw material.

[0004] In view of the above-mentioned defects, the present design person actively researches and innovates, so as to create a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives, so that it has more industrial utilization value. SUMMARY

[0005] To solve the above technical problems, the purpose of the present application is to provide a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives.

[0006] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0007] A method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives, comprising the following steps in sequence:

[0008] Step S1, dissolve 2-halogen-1H-imidazole and potassium carbonate in acetone, and slowly add 2-(trimethylsilyl)ethoxymethyl chloride to the solution, stir the mixture at room temperature overnight, concentrate the reaction liquid to remove acetone, dilute with water and extract with ethyl acetate, dry the combined organic layer with sodium sulfate, filter and concentrate, and purify the crude product by column chromatography to obtain 2-halogen-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole;

[0009] Step S2, the o-amino halogenated benzene compound, bis(pinacolato)diboron, potassium acetate and palladium catalyst are dissolved in 1,4-dioxane, the reaction solution is stirred at 105℃ under nitrogen overnight, the reaction solution is diluted with water, extracted with ethyl acetate, the combined organic layer is dried over anhydrous sodium sulfate, filtered and concentrated, the crude product is purified by column chromatography, and the product o-aminobenzene boronic acid pinacol ester is obtained;

[0010] Step S3, 2-halo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole, o-aminobenzene boronic acid pinacol ester, palladium catalyst, cesium carbonate are dissolved in 1,4-dioxane / water, the reaction solution is stirred at 110℃ in a sealed tube under nitrogen overnight, the reaction solution is diluted with water, extracted with ethyl acetate, the combined organic layer is dried over anhydrous sodium sulfate, filtered and concentrated, the crude product is purified by thin layer chromatography, and o-amino(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)benzene is obtained.

[0011] Step S4, o-amino(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)benzene is dissolved in solvent 1 and an acidic reagent 1 is added, the mixture is stirred at 0-100℃ for 1 hour, the reaction solution is concentrated, the pH is adjusted to 8 with a basic reagent, and extracted with DCM / MeOH=10 / 1, the combined organic layer is dried over anhydrous sodium sulfate, filtered and concentrated, the crude product is purified by thin layer chromatography, and the target product 5,6-dihydroimidazo[1,2-c]quinazoline is obtained.

[0012] As a further improvement of the present application, the halogenated element is iodine, bromine, or chlorine.

[0013] As a further improvement of the present application, the palladium catalyst in step S2 and step S3 is Pd(dppf)Cl2 or Pd(dppf)Cl2.CH2Cl2 or Pd(PPh3)4 or Pd(dtbpf)Cl2 or Pd(OAc)2.

[0014] As a further improvement of the present application, the solvent 1 in step S4 is dichloromethane or dichloroethane or tetrahydrofuran or 1,4-dioxane or N,N-dimethylformamide or N,N-dimethylacetamide or toluene.

[0015] As a further improvement of the present application, the solvent 1 in step S4 is dichloromethane.

[0016] As a further improvement of the present application, the acidic reagent 1 in step S4 is hydrochloric acid or sulfuric acid or nitric acid or trifluoroacetic acid or trifluoroacetic anhydride or acetic acid or acetic anhydride or formic acid or p-toluenesulfonic acid, and the basic reagent in step S4 is saturated sodium bicarbonate solution.

[0017] As a further improvement of the present application, the acid reagent in step S4 is hydrochloric acid or trifluoroacetic acid.

[0018] As a further improvement of the present application, the mixture in step S4 is stirred at 40-60°C for 1 hour.

[0019] As a further improvement of the present application, the mixture in step S4 is stirred at 50°C for 1 hour.

[0020] As a further improvement of the present application, the column chromatography in step S1 is ethyl acetate / petroleum ether = 1 / 8; the column chromatography in step S2 is ethyl acetate / petroleum ether = 1 / 20; the thin layer chromatography in step S3 is petroleum ether: ethyl acetate = 2:1; and the thin layer chromatography in step S4 is petroleum ether: ethyl acetate = 1:1.

[0021] By the above scheme, the present application has at least the following advantages:

[0022] The present application provides a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives, which has simple synthesis operation, mild reaction condition, improved synthesis efficiency and reduced synthesis cost.

[0023] The above description is only a summary of the technical solutions of the present application. In order to more clearly understand the technical means of the present application, and to implement the content of the description, the following will be described in detail with the preferred embodiments of the present application and with the accompanying drawings. BRIEF DESCRIPTION OF DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments. It should be understood that the following drawings only show some embodiments of the present application, and therefore should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can also be obtained without creative labor on the basis of these drawings.

[0025] Figure 1 is the reaction equation of the first synthesis process in the prior art;

[0026] Figure 2 is the reaction equation of the second synthesis process in the prior art;

[0027] Figure 3 is the reaction equation of the third synthesis process in the prior art;

[0028] Figure 4 is the reaction equation of the fourth synthesis process in the prior art;

[0029] Figure 5 is the reaction equation of the fifth synthesis process in the prior art;

[0030] Figure 6 is the structural formula of the target product of the present application, wherein R1-R2 represent hydrogen, R3-R6 represent hydrogen, methyl, halogen, ester group, trifluoromethyl or other electron-withdrawing or electron-donating groups;

[0031] Figure 7 is the reaction equation of the synthesis process of the target product of the present application;

[0032] Figure 8 is the reaction equation of step S1 in the first embodiment of the present application;

[0033] Figure 9 is the reaction equation of step S2 in the first embodiment of the present application;

[0034] Figure 10 is the reaction equation of step S3 in the first embodiment of the present application;

[0035] Figure 11 is the reaction equation of step S4 in the first embodiment of the present application;

[0036] Figure 12 is the reaction equation of the synthesis process of the second embodiment of the present application;

[0037] Figure 13 is the reaction equation of the synthesis process of the third embodiment of the present application;

[0038] Figure 14 is the reaction equation of the synthesis process of the fourth embodiment of the present application. DETAILED DESCRIPTION

[0039] The specific embodiments of the present application will be further described in conjunction with the accompanying drawings and examples. The following examples are used to illustrate the present application, but are not intended to limit the scope of the present application.

[0040] In order to enable persons skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. The components of the embodiments of the present application described and shown in the accompanying drawings can be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present application provided in the accompanying drawings is not intended to limit the scope of the claimed present application, but only represents selected embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present application.

[0041] EMBODIMENT

[0042] As Figures 6-14 shown,

[0043] A method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and derivatives thereof, comprising the following steps in sequence:

[0044] Step S1, dissolve 2-halogen-1H-imidazole and potassium carbonate in acetone, and slowly add 2-(trimethylsilyl)ethoxymethyl chloride to the solution, stir the mixture at room temperature overnight, concentrate the reaction solution to remove acetone, dilute with water and extract with ethyl acetate, dry the combined organic layers with sodium sulfate, filter and concentrate, purify the crude product by column chromatography to obtain 2-halogen-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole;

[0045] Step S2, dissolve the o-amino halogenated benzene compound, pinacol diboronic acid, potassium acetate and palladium catalyst in 1,4-dioxane, stir the reaction solution at 105°C under nitrogen overnight, dilute the reaction solution with water and extract with ethyl acetate, dry the combined organic layers with anhydrous sodium sulfate, filter and concentrate, purify the crude product by column chromatography to obtain the product o-amino benzene compound pinacol borate;

[0046] Step S3, dissolve 2-halogen-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole, o-amino benzene compound pinacol borate, palladium catalyst, cesium carbonate in 1,4-dioxane / water, stir the reaction solution at 110°C in a sealed tube under nitrogen overnight, dilute the reaction solution with water and extract with ethyl acetate, dry the combined organic layers with anhydrous sodium sulfate, filter and concentrate, purify the crude product by thin layer chromatography to obtain o-amino(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)benzene compound;

[0047] Step S4, dissolve the o-amino(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)benzene compound in solvent one and add acidic reagent one, stir the mixture at 0-100°C for 1 hour, concentrate the reaction solution, adjust the pH to 8 with basic reagent, and extract with DCM / MeOH=10 / 1, dry the combined organic layers with anhydrous sodium sulfate, filter and concentrate, purify the crude product by thin layer chromatography to obtain the target product 5,6-dihydroimidazo[1,2-c]quinazoline compound.

[0048] Preferably, the halogen element is iodine, bromine, chlorine.

[0049] Preferably, the palladium catalyst in step S2 and step S3 is Pd(dppf)Cl2 or Pd(dppf)Cl2.CH2Cl2 or Pd(PPh3)4 or Pd(dtbpf)Cl2 or Pd(OAc)2.

[0050] Preferably, the solvent one in step S4 is dichloromethane or dichloroethane or tetrahydrofuran or 1,4-dioxane or N,N-dimethylformamide or N,N-dimethylacetamide or toluene.

[0051] Preferably, the solvent one in step S4 is dichloromethane.

[0052] Preferably, the acid reagent one in step S4 is hydrochloric acid or sulfuric acid or nitric acid or trifluoroacetic acid or trifluoroacetic anhydride or acetic acid or acetic anhydride or formic acid or p-toluenesulfonic acid, and the basic reagent in step S4 is saturated sodium bicarbonate solution.

[0053] Preferably, the acid reagent one in step S4 is hydrochloric acid or trifluoroacetic acid.

[0054] Preferably, the mixture in step S4 is stirred at 40-60℃ for 1 hour.

[0055] Preferably, the mixture in step S4 is stirred at 50℃ for 1 hour.

[0056] Preferably, the column chromatography one in step S1 is ethyl acetate / petroleum ether = 1 / 8; the column chromatography two in step S2 is ethyl acetate / petroleum ether = 1 / 20; the thin layer chromatography one in step S3 is petroleum ether: ethyl acetate = 2:1; and the thin layer chromatography two in step S4 is petroleum ether: ethyl acetate = 1:1.

[0057] The principle of the synthesis method of 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives according to the present application is as follows:

[0058] According to the present application, the target product is obtained by reacting boric acid or borate with (trimethylsilyl)ethoxymethyl-protected imidazole halide and then ring-closing under acidic conditions.

[0059] As shown in Figure 8 and Figure 11 , the first embodiment of the present application is as follows:

[0060] Step S1:

[0061] Dissolve 2-bromo-lH-imidazole (2 g, 13.6 mmol) and potassium carbonate (3.76 g, 27.2 mmol,) in acetone (20 mL), and slowly add 2-(trimethylsilyl)ethoxymethyl chloride (3.4 g, 20.4 mmol) to the solution. Stir the mixture at room temperature overnight. Concentrate the reaction to remove acetone, dilute with water (50 mL) and extract with ethyl acetate (50 mL x 3). Dry the combined organic layers over sodium sulfate, filter and concentrate. Purify the crude product by column chromatography one (gradient: ethyl acetate / petroleum ether = 1 / 8) to give 2-bromo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole (2.28 g, yield 60.5%) as a clear oil.

[0062] LCMS: m / z 277.15 [M+H]

[0063] 1 H NMR (400 MHz, Chloroform-d) δ 7.10 (d, J = 1.6 Hz, 1H), 7.04 (dd, J = 3.6, 1.6 Hz, 1H), 5.27 (s, 2H), 3.57 - 3.50 (m, 2H), 0.96 - 0.86 (m, 2H), -0.01 (s, 9H).

[0064] Step S2:

[0065] Dissolve 2-bromo-4-methylaniline (300 mg, 1.6 mmol), bis(pinacolato)diboron (532.3 mg, 2.1 mmol), potassium acetate (633 mg, 6.4 mmol) and Pd(dppf)Cl2(58.5 mg, 0.08 mmol) in 1,4-dioxane (5 mL) and stir the reaction at 105 °C under nitrogen overnight. Dilute the reaction with water (50 mL) and extract with ethyl acetate (50 mL x 3). Dry the combined organic layers over anhydrous sodium sulfate, filter and concentrate. Purify the crude product by column chromatography two (gradient: ethyl acetate / petroleum ether = 1 / 20) to give the product 4-methyl-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline (100 mg, yield 27%) as a yellow solid.

[0066] LCMS: m / z 234.20 [M+H]

[0067] 1H NMR (400 MHz, Chloroform-d) δ 7.42 (s, 1H), 7.03 (dd, J = 8.0, 2.0Hz, 1H), 6.55 (d, J = 8.2 Hz, 1H), 2.21 (s, 3H), 1.34 (s, 12H).

[0068] Step S3:

[0069] Step S3:

[0070] LCMS: m / z 304.20 [M+H]

[0071] 1 H NMR (400 MHz, Chloroform-d) δ 7.21 – 7.15 (m, 2H), 7.11 (d, J =1.6 Hz, 1H), 7.01 (d, J = 8.2 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1H), 5.23 (s,2H), 3.53 – 3.47 (m, 2H), 2.26 (s, 3H), 0.93 – 0.88 (m, 2H), -0.01 (s, 9H).

[0072] Step S4:

[0073] To a solution of 4-methyl-2-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2- yl)aniline (66 mg, 0.36 mmol) in DCM (2 mL) was added TFA (1 mL). The mixture was stirred at 50 °C for 1 h. The reaction was concentrated, the pH was adjusted to 8 with saturated sodium bicarbonate solution, and extracted with DCM / MeOH = 10 / 1 (20 mL x 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by thin layer chromatography (petroleum ether: ethyl acetate = 1:1) to give 9-methyl-5,6-dihydroimidazo[l,2-c]quinazoline as a yellow oil (12 mg, 29.8% yield).

[0074] wherein the above DCM is dichloromethane and the above TFA is trifluoroacetic acid.

[0075] LCMS: m / z 186.20 [M+H]

[0076] 1 H NMR (400 MHz, Chloroform-d) δ 7.82 (s, 1H), 7.18 (s, 1H), 7.02 (d, J = 8.6 Hz, 1H), 6.88 (d, J = 1.4 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 5.30 (s,2H), 3.49 (s, 1H), 2.32 (s, 3H).

[0077] As Figure 12 , the second embodiment of the present application:

[0078] First, 4-chloro-2-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)aniline was obtained.

[0079] LCMS: m / z 324.30 [M+H]

[0080] 1 H NMR (400 MHz, Chloroform-d) δ 7.34 (s, 1H), 7.22 (s, 1H), 7.15(dd, J = 9.4, 1.8 Hz, 2H), 6.72 (d, J = 8.6 Hz, 1H), 5.20 (s, 2H), 3.58 –3.47 (m, 2H), 0.97 – 0.90 (m, 2H), -0.00 (s, 9H).

[0081] The target product 9-chloro-5,6-dihydroimidazo[l,2-c]quinazoline is finally obtained.

[0082] LCMS: m / z 206.15 [M+H]

[0083] 1 H NMR (400 MHz, DMSO-d6) δ 7.61 (d, J = 2.6 Hz, 1H), 7.22 (d, J =1.2 Hz, 1H), 7.16 (dd, J = 8.6, 2.6 Hz, 1H), 7.09 (s, 1H), 6.85 (s, 1H), 6.83(s, 1H), 5.32 (d, J = 1.4 Hz, 2H).

[0084] As Figure 13 the third embodiment of the present application:

[0085] Firstly, methyl 3-amino-4-(l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2- yl)benzoate is obtained.

[0086] LCMS: m / z 348.10[M+H]

[0087] 1 H NMR (400 MHz, Chloroform-d) δ 7.52 (d, J = 8.2 Hz, 1H), 7.45 (d, J= 1.6 Hz, 1H), 7.41 (dd, J = 8.0, 1.6 Hz, 1H), 7.21 (s, 1H), 7.14 (d, J = 1.4Hz, 1H), 5.23 (s, 2H), 3.91 (s, 3H), 3.55 (t, J = 8.2 Hz, 2H), 0.95 – 0.89(m, 2H), -0.00 (s, 9H).

[0088] The target product 5,6-dihydroimidazo[l,2-c]quinazoline-8-carboxylic acid methyl ester is finally obtained.

[0089] LCMS: m / z 230.10 [M+H]

[0090] 1H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 8.0 Hz, 1H), 7.62 (dd, J = 8.0, 1.6 Hz, 1H), 7.46 (d, J = 1.6 Hz, 1H), 7.23 (d, J = 1.2 Hz, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.40 (d, J = 2.2 Hz, 2H), 4.37 (s, 1H), 3.91 (s, 3H).

[0091] As Figure 14 the fourth embodiment of the present application:

[0092] Firstly, 4-(trifluoromethyl)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)aniline was obtained.

[0093] LCMS: m / z 358.15 [M+H]

[0094] 1 H NMR (400 MHz, DMSO-d6) δ 7.82 (t, J = 1.6 Hz, 1H), 7.48 (d, J =1.4 Hz, 1H), 7.40 (dd, J = 8.6, 2.2 Hz, 1H), 7.11 (d, J = 1.4 Hz, 1H), 6.91(d, J = 8.6 Hz, 1H), 6.71 (s, 2H), 5.24 (s, 2H), 3.59 – 3.53 (m, 2H), 0.90 –0.83 (m, 2H), -0.04 (s, 9H).

[0095] Finally, the target product 9-(trifluoromethyl)-5,6-dihydroimidazo[1,2-c]quinazoline was obtained.

[0096] LCMS: m / z 240.05 [M+H]

[0097] 1H NMR (400 MHz, DMSO-d6) δ 7.91 - 7.83 (m, 1H), 7.42 (dd, J = 8.6, 2.2 Hz, 1H), 7.32 (s, 1H), 7.21 (d, J = 1.2 Hz, 1H), 7.10 (d, J = 1.4 Hz, 1H), 6.94 (d, J = 8.6 Hz, 1H), 5.43 (d, J = 1.6 Hz, 2H).

[0098] In summary, the present application relates to a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives. The method comprises the following steps: reacting boronic acid or boron ester with (trimethylsilyl)ethoxymethyl protected imidazole halide, and then closing the ring under acidic conditions to obtain the target product. The present application provides a method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives. The method has simple synthesis operation, mild reaction conditions, improved synthesis efficiency and reduced synthesis cost.

[0099] Although the present application is disclosed as above, the present application is not limited thereto. Any person skilled in the art can make various changes and modifications without departing from the spirit and scope of the present application. Therefore, the protection scope of the present application should be defined by the scope defined in the claims.

[0100] The above description is only the preferred embodiments of the present application and is not used to limit the present application. It should be pointed out that, for ordinary skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present application. These improvements and modifications should also be considered as the protection scope of the present application.

Claims

1. A method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives, characterized in that: The following steps are included in sequence: Step S1: 2-halogeno-1H-imidazole and potassium carbonate are dissolved in acetone, and 2-(trimethylsilyl)ethoxymethyl chloride is slowly added to the solution. The mixture is stirred at room temperature overnight. The reaction solution is concentrated to remove acetone, diluted with water, and extracted with ethyl acetate. The combined organic layer is dried over sodium sulfate, filtered, and concentrated. The crude product is purified by column chromatography to obtain 2-halogeno-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole; Step S2, dissolving an o-aminohalogenated benzene compound, biboronic acid pinacol ester, potassium acetate and a palladium catalyst in a 1,4-dioxane reaction solution at 105° C. and stirring overnight under nitrogen, diluting the reaction solution with water and extracting with ethyl acetate, drying the combined organic layer over anhydrous sodium sulfate, filtering and concentrating, and purifying the crude product by column chromatography to obtain a product, biboronic acid pinacol ester of an o-aminobenzene compound, wherein the molecular structure of the biboronic acid pinacol ester is: Wherein, R3-R6 represent hydrogen, methyl, halogen, trifluoromethyl; Step S3: 2-halo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole, pinacol borate of an o-aminobenzene compound, a palladium catalyst, and cesium carbonate are dissolved in 1,4-dioxane / water. The reaction solution is stirred overnight at 110° C. in a sealed tube under nitrogen. The reaction solution is diluted with water and extracted with ethyl acetate. The combined organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by thin layer chromatography to obtain an o-amino(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)benzene compound. The molecular structure of the o-amino(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)benzene compound is: Wherein, R1-R2 represent hydrogen, R3-R6 represent hydrogen, methyl, halogen, trifluoromethyl; Step S4: dissolving an o-amino(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)benzene compound in solvent one and adding an acidic reagent one. The mixture is stirred at 0-100° C. for 1 hour. The reaction solution is concentrated, the pH is adjusted to 8 with an alkaline reagent, and the mixture is extracted with DCM / MeOH=10 / 1. The combined organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product is purified by thin layer chromatography two to obtain the target product 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives. The molecular structure of the 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives is: Wherein, R1-R2 represent hydrogen, and R3-R6 represent hydrogen, methyl, halogen, or trifluoromethyl.

2. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 1, characterized in that: Halogenated elements include iodine, bromine and chlorine.

3. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 1, characterized in that: The palladium catalyst in step S2 and step S3 is Pd(dppf)Cl2 or Pd(dppf)Cl2.CH2Cl2 or Pd(PPh3)4 or Pd(dtbpf)Cl2 or Pd(OAc)2.

4. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 1, characterized in that: In step S4, the first solvent is dichloromethane, dichloroethane, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, or toluene.

5. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 4, characterized in that: In step S4, the first solvent is dichloromethane.

6. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 1, characterized in that: The acidic reagent 1 in step S4 is hydrochloric acid, sulfuric acid, nitric acid, trifluoroacetic acid, trifluoroacetic anhydride, acetic acid, acetic anhydride, formic acid, or p-toluenesulfonic acid, and the alkaline reagent in step S4 is saturated sodium bicarbonate solution.

7. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 6, characterized in that: In step S4, the acidic reagent 1 is hydrochloric acid or trifluoroacetic acid.

8. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 1, characterized in that: In step S4, the mixture is stirred at 40-60° C. for 1 hour.

9. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives as claimed in claim 8, characterized in that: In step S4, the mixture is stirred at 50° C. for 1 hour.

10. The method for synthesizing 5,6-dihydroimidazo[1,2-c]quinazoline and its derivatives according to claim 1, characterized in that: In step S1, the first column chromatography was performed with ethyl acetate / petroleum ether = 1 / 8; in step S2, the second column chromatography was performed with ethyl acetate / petroleum ether = 1 / 20; in step S3, the first thin layer chromatography was performed with petroleum ether:ethyl acetate = 2:1; in step S4, the second thin layer chromatography was performed with petroleum ether:ethyl acetate = 1:1.

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