A method for preparing a dihydroquinazoline compound

Abstract

The application provides a preparation method of a dihydroquinazoline compound and belongs to the technical field of organic synthesis. 1 comprises hydrogen, methyl, tert-butyl, methoxy or halogen; R 2 comprises phenyl; R 3 comprises phenyl; R 4 comprises phenyl, p-tolyl, p-methoxyphenyl, o-tolyl, p-fluorophenyl, p-chlorophenyl, naphthyl, pyridyl or thienyl; Ar comprises phenyl, naphthyl or pyridyl; R 5 comprises phenyl, cyclopropyl, cyclohexyl or [1,1'-biphenyl]-4-yl. The preparation method provided by the application has the advantages of short reaction route, no need to add a transition metal catalyst, good functional group compatibility, high yield, high production efficiency and green environmental protection.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a preparation method of a dihydroquinazoline compound. BACKGROUND

[0002] Quinazoline compounds are concerned by the organic synthesis field due to their wide pharmacological activities. Among them, 1,2-dihydroquinazoline compounds also have rich pharmacological effects, such as anti-inflammatory and antibacterial functions, and can also be used as nitric oxide synthase (NOS) inhibitors and trypanothione reductase (TR) inhibitors.

[0003] At present, a variety of methods for synthesizing dihydroquinazoline compounds have been reported. Among them, the synthesis method of 1,2-dihydroquinazoline is usually to react 2-aminobenzophenone or 2-aminoacetophenone with ketone, diketone, benzaldehyde, benzylamine or aldehyde, etc.

[0004] For example, Strekowski group (Strekowski, L.;Cegla, M. T.;Kong, S.-B.;Harden, D. B., Synthesis of 2,2,4-trisubstituted-1,2-dihydroquinazolines. J. Heterocyclic. Chem. 1989, 26, 923-928.) reported that o-aminobenzonitrile was condensed with aldehyde to obtain imine, which was then reacted with alkyl lithium compound, followed by the formation of imine under the action of DDQ, and then reacted with alkyl lithium compound, followed by the removal of water to obtain 2,2,4-trisubstituted-1,2-dihydroquinazoline, and the reaction route is as shown in formula 1.

[0005] However, the substrate universality of this method is poor, and the reaction steps are complicated.

[0006]

[0007] Bergman group (Wiklund, P.;Bergman, J., Ring forming reactions of imines of 2-aminobenzaldehyde and related compounds. Org. Biomol. Chem. 2003, 1, 367-372.) reported that o-aminobenzonitrile was reduced to imine anion under the action of diisobutylaluminum hydride (DIBAL-H), and then captured by benzaldehyde to form dihydroquinazoline compound, and the reaction route is as shown in formula 2. However, the diisobutylaluminum hydride used in this method needs to be reacted under anhydrous and low temperature conditions, and the reaction conditions are harsh.

[0008]

[0009] Prajapati group (Sarma, R.; Prajapati, D., Microwave-promoted efficient synthesis of dihydroquinazolines. Green Chem. 2011, 13, 718-722.) reported a three-component one-pot synthesis of 2,4-disubstituted-1,2-dihydroquinazolines and a small amount of 2,4-disubstituted quinazolines from aldehyde, urea and substituted 2-aminobenzophenone in a microwave vessel under 540 W irradiation without solvent and catalyst, reaction route as shown in formula 3. However, the reaction product is not a single structure, there is also a small amount of quinazoline by-product, poor selectivity, need to be carried out under microwave instrument, the amount of microwave reaction is limited, not conducive to large-scale production.

[0010]

[0011] Group (Kohlmann, R.; Stopka, T.; Richter, H.; Garcia O., Iron-Catalyzed Oxidative Tandem Reactions with TEMPO Oxoammonium Salts: Synthesis of Dihydroquinazolines and Quinolines. J. Org. Chem. 2013, 78, 6050-6064.) reported the use of TEMPO oxoammonium salt as a non-toxic, efficient and mild oxidant, easily available Fe(OTf)2catalyst with T + BF4 - As a formal hydrogen acceptor, simple N-alkyl aniline is directly polymerized into a series of dihydroquinazolines, reaction route as shown in formula 4. However, this method needs to use metal catalyst, resulting in cumbersome post-processing, and is not environmentally friendly.

[0012]

[0013] Derabli group (Derabli, C.;Boulcina, R.;Kirsch, G.;Carboni, B.;Debache, A., A DMAP-catalyzed mild and efficient synthesis of 1,2-dihydroquinazolines via a one-pot three-component protocol. Tetrahedron Lett. 2014, 55, 200-204.) reported that 1,2-dihydroquinazoline compounds were synthesized using DMAP (4-(N,N-dimethylamino) pyridine) as catalyst, aldehyde compounds, substituted 2-amino benzophenone and ammonium acetate as raw materials, and the reaction route is shown in formula 5. However, this method synthesizes a mixture of dihydroquinazoline and quinazoline, and the selectivity is poor.

[0014]

[0015] Srivastava group (Srivastava, V., Hydrotalcite Clay+[TBA][OH] Ionic Liquid Combination for Selective Dihydroquinazolines. Curr. Organocatalysis 2019, 6, 44-51.) reported that 18 kinds of 1,2-dihydroquinazoline derivatives were synthesized by three-component one-pot method using aromatic aldehyde, 2-amino benzophenone and ammonium acetate as raw materials, and the reaction route is shown in formula 6. However, the substrate of 2-amino benzophenone in this method is limited, and the reaction only proceeds when the substituent X is -Cl and -NO2, and a small amount of quinazoline by-product is also mixed in the product.

[0016]

[0017] The above synthesis methods have problems of multiple by-products, low product selectivity, complicated reaction route, catalyst recovery, etc. Therefore, it is necessary to develop a simple, efficient and transition metal-free method for synthesizing quinazoline. SUMMARY

[0018] Therefore, the purpose of the present application is to provide a preparation method of dihydroquinazoline compound. The preparation method provided by the present application does not need to add transition metal catalyst, has short reaction route, good functional group compatibility, high yield and is green and environmentally friendly.

[0019] To achieve the above object, the present application provides the following technical solutions.

[0020] The present application provides a preparation method of a dihydroquinazoline compound, comprising the following steps:

[0021] The imine compound, the o-iodoaniline compound, the organic base and the oxygen-containing organic solvent are mixed, and a series reduction / radical coupling / S N 2 reaction / oxidation reaction to obtain a dihydroquinazoline compound;

[0022] The dihydroquinazoline compound has the structure shown in formula I or formula II:

[0023]

[0024] In the formula I, R 1 including hydrogen, methyl, tert-butyl, methoxy or halogen; R 2 including phenyl; R 3 including phenyl; R 4 including phenyl, p-tolyl, p-methoxyphenyl, o-tolyl, p-fluorophenyl, p-chlorophenyl, naphthyl, pyridyl or thienyl; Ar includes phenyl, naphthyl or pyridyl;

[0025] In the formula II, R 5 including phenyl, cyclopropyl, cyclohexyl or [1,1'-biphenyl]-4-yl;

[0026] The imine compound is

[0027] When the imine compound is , the o-iodoaniline compound is The R 1 ~R 4 is the same as R 1 ~R 4 in the formula I;

[0028] When the imine compound is , the o-iodoaniline compound is o-iodoaniline, and the R 5 is the same as R 5 in the formula II.

[0029] Preferably, the R 1 includes 6-methyl, 6-tert-butyl, 8-methoxy, 6-halogen or 7-halogen.

[0030] Preferably, the dihydroquinazoline compound has the structure shown in any one of formula I-1~I-17 and formula II-1~II-4:

[0031]

[0032]

[0033] Preferably, the molar ratio of the imine compound to the o-iodoaniline compound is 1.5-3: 1-1.5.

[0034] Preferably, the organic base comprises one or more of potassium bis(trimethylsilyl)amide, potassium tert-butoxide and sodium bis(trimethylsilyl)amide.

[0035] Preferably, the molar ratio of the o-iodoaniline compound to the organic base is 1-1.5: 2.5-4.

[0036] Preferably, the oxygen-containing organic solvent comprises one or more of 1,4-dioxane, tetrahydrofuran, cyclopentyl methyl ether, methyl tert-butyl ether and dimethyl sulfoxide.

[0037] Preferably, the tandem reduction / radical coupling / S N The temperature of the reaction / oxidation reaction is 95-100℃, and the time is 11-12h.

[0038] The application provides a preparation method of a dihydroquinazoline compound. The application takes an imine compound and an o-iodoaniline compound as raw materials, and a dihydroquinazoline compound can be synthesized through one-step reaction in the presence of a base and an oxygen-containing organic solvent. The preparation method provided by the application has the characteristics of short reaction route, high yield of target product, no need to add a transition metal catalyst, excellent functional group compatibility, good method universality and green environmental protection. DETAILED DESCRIPTION

[0039] The application provides a preparation method of a dihydroquinazoline compound, comprising the following steps:

[0040] The imine compound, the o-iodoaniline compound, the organic base and the oxygen-containing organic solvent are mixed to perform a tandem reduction / radical coupling / S N 2 reaction / oxidation reaction, to obtain a dihydroquinazoline compound.

[0041] The dihydroquinazoline compound has the structure shown in formula I or formula II:

[0042]

[0043] In the formula I, R 1 comprises hydrogen, methyl, tert-butyl, methoxy or halogen; R 2 comprises phenyl; R 3 comprises phenyl; R 4include phenyl, p-tolyl, p-methoxyphenyl, o-tolyl, p-fluorophenyl, p-chlorophenyl, naphthyl, pyridyl, or thienyl; Ar includes phenyl, naphthyl, or pyridyl;

[0044] in the formula II, R 5 include phenyl, cyclopropyl, cyclohexyl, or [1,1'-biphenyl]-4-yl;

[0045] the imine compound is

[0046] when the imine compound is the o-iodoaniline compound is R 1 ~R 4 is the same as R 1 ~R 4 in the formula I;

[0047] when the imine compound is the o-iodoaniline compound is o-iodoaniline, and R 5 is the same as R 5 in the formula II.

[0048] In the present application, all of the raw material components are commercially available products well known to those skilled in the art, unless otherwise specified.

[0049] In the present application, R 1 preferably includes 6-methyl, 6-t-butyl, 8-methoxy, 6-halo, or 7-halo; the halo preferably includes fluorine, chlorine, or bromine, the 6-halo more preferably includes 6-chloro or 6-bromo, and the 7-halo more preferably includes 7-fluoro.

[0050] In the present application, in the formula II, R 5 include phenyl, cyclopropyl, cyclohexyl, or [1,1'-biphenyl]-4-yl.

[0051] In the present application, the dihydroquinazoline compound preferably has a structure represented by any one of the formulae I-1 to I-17 and the formulae II-1 to II-4:

[0052]

[0053] In the present application, the (Ketoimine compounds) preferably include N-benzyl-1,1-diphenylmethyleneimine, N-(4-methylbenzyl)-1,1-diphenylmethyleneimine, N-(4-methoxybenzyl)-1,1-diphenylmethyleneimine, N-(2-methylbenzyl)-1,1-diphenylmethyleneimine, N-(4-fluorobenzyl)-1,1-diphenylmethyleneimine, N-(4-chlorobenzyl)-1,1-diphenylmethyleneimine, N-(naphthyl-2-ylmethyl)-1,1-diphenylmethyleneimine, 1,1-diphenyl-N-(pyridin-3-ylmethyl)methyleneimine, or 1,1-diphenyl-N-(thiophene-2-ylmethyl)methyleneimine.

[0054] In this invention, the (Aldehydeimine compounds) preferably include N-(9H-fluoren-9-yl)-1-phenylmethylimine, 1-isopropyl-N-(9H-fluoren-9-yl)methylimine, 1-cyclohexyl-N-(9H-fluoren-9-yl)methylimine or 1-([1,1'-biphenyl]-4-yl)-N-(9H-fluoren-9-yl)methylimine.

[0055] In this invention, the Preferred ingredients include 2-iodoaniline, 2-iodo-4-methylaniline, 2-iodo-4-tert-butylaniline, 2-iodo-4-methoxyaniline, 2-iodo-4-trifluoromethoxyaniline, 6-iodobenzo[d][1,3]dioxane-5-amine, 2-iodo-6-methoxyaniline, 5-fluoro-2-iodoaniline, 4-chloro-2-iodoaniline, 4-bromo-2-iodoaniline, 1-iodonaphthalene-2-amine, 4-iodopyridine-3-amine, or 5-iodoquinoline-6-amine.

[0056] In this invention, the molar ratio of the imine compound to the o-iodoaniline compound is preferably 1.5-3:1-1.5, more preferably 2-2.5:1-1.2.

[0057] In this invention, the organic base preferably comprises one or more of potassium bis(trimethylsilyl)amino, potassium tert-butoxide, and sodium bis(trimethylsilyl)amino, more preferably potassium bis(trimethylsilyl)amino, potassium tert-butoxide, or sodium bis(trimethylsilyl)amino. In this invention, the molar ratio of the o-iodoaniline compound to the organic base is preferably 1–1.5:2.5–4, more preferably 1–1.2:3–3.5.

[0058] In the present application, the oxygen-containing organic solvent preferably comprises one or more of 1,4-dioxane, tetrahydrofuran, cyclopentyl methyl ether, methyl tert-butyl ether and dimethyl sulfoxide, more preferably comprises 1,4-dioxane, tetrahydrofuran, cyclopentyl methyl ether, methyl tert-butyl ether or dimethyl sulfoxide; the oxygen-containing organic solvent is preferably anhydrous oxygen-containing organic solvent. In the present application, the mass ratio of the o-iodoaniline compound to the volume of the oxygen-containing organic solvent is preferably 1 g: 40-45 mL, more preferably 1 g: 40-42 mL.

[0059] In the present application, the mixing is preferably: dissolving the imine compound and the o-iodoaniline compound in the oxygen-containing organic solvent, and mixing the obtained mixture with the organic base under heat. In the present application, the temperature of the heat mixing is preferably 60-120°C, more preferably 80-100°C; the present application does not have special limitations on the manner of the mixing, and the raw materials can be mixed uniformly, for example, by stirring. In the present application, the mixing is preferably carried out under a protective atmosphere, and the protective atmosphere preferably comprises nitrogen, argon or helium.

[0060] In the present application, the tandem reduction / free radical coupling / S N The temperature of the reaction / oxidation reaction is preferably 95-100°C, more preferably 98-100°C; the tandem reduction / free radical coupling / S N The reaction / oxidation reaction time is preferably 11-12 h, more preferably 11.5-12 h; the tandem reduction / free radical coupling / S N The reaction / oxidation reaction is preferably carried out in a closed, stirred and protective atmosphere; the protective atmosphere preferably comprises nitrogen, argon or helium. The synthesis method provided by the present application has mild reaction conditions. In the present application, the tandem reduction / free radical coupling / S N The reaction occurring during the reaction / oxidation reaction is shown in formula (1):

[0061]

[0062] The tandem reduction / free radical coupling / S N After the reaction / oxidation reaction, the present application preferably further comprises post-treatment, and the post-treatment preferably comprises: after the obtained tandem reduction / free radical coupling / S N2 The reaction is quenched by adding water, and then diluted with ethyl acetate, and then solid-liquid separation is performed, the liquid component obtained is concentrated, and column chromatography separation is performed to obtain the dihydroquinazoline compound. In the present application, the water is preferably added dropwise, and the amount of water used is not particularly limited in the present application, and the reaction can be quenched. In the present application, the ratio of the amount of substance of the o-iodoaniline compound to the volume of ethyl acetate is preferably 1 mmol: 10-20 mL, and more preferably 1 mmol: 12-15 mL. The solid-liquid separation is not particularly limited in the present application, and a solid-liquid separation method known to those skilled in the art can be used, for example, suction filtration. The concentration is not particularly limited in the present application, and a concentration method known to those skilled in the art can be used. In the present application, the eluent used in the column chromatography separation preferably comprises petroleum ether-ethyl acetate mixed solvent, and the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate mixed solvent is preferably 10-30: 1.

[0063] The technical solutions in the present application will be described clearly and completely in combination with the embodiments in the present application. Obviously, the described embodiments are only some of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of protection of the present application.

[0064] Embodiment 1

[0065] Synthesis of 2,2,4-triphenyl-1,2-dihydroquinazoline (I-1)

[0066]

[0067] The ketimine compound (N-benzyl-1,1-diphenylmethanimine) and the o-iodoaniline compound (2-iodoaniline) are dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, mixed uniformly at 100°C by adding potassium bis(trimethylsilyl)amide, sealed under a nitrogen atmosphere, and reacted at 100°C under stirring for 12 h, the reaction is quenched by adding water, diluted with ethyl acetate, and then suction filtered on a 2 cm thick silica gel pad, the reaction bottle and the silica gel pad are washed with ethyl acetate for 3 times, and all the filtrates are concentrated under reduced pressure, and the crude product is separated by column chromatography on inactivated silica gel to obtain 2,2,4-triphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline and the potassium bis(trimethylsilyl)amide is 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane is 1 g:40 mL, the ratio of the amount of the o-iodoaniline compound to the ethyl acetate used for dilution is 0.2 mmol:3 mL, and the eluent used in the column chromatography is petroleum ether-ethyl acetate (volume ratio is 30:1).

[0068] 1H NMR spectrum of 2,2,4-triphenyl-1,2-dihydroquinazoline: 1 H NMR (600MHz, Chloroform-d) δ: 7.54 (dd, J=45.8, 6.4Hz, 6H), 7.41 (d, J=5.3Hz, 3H), 7.33-7. 17(m,7H),7.04(d,J=7.8Hz,1H),6.73(d,J=8.0Hz,1H),6.60(t,J=7.6Hz,1H),4.65(s,1H);

[0069] Carbon NMR spectrum of 2,2,4-triphenyl-1,2-dihydroquinazoline: 13 C NMR(150MHz,Chloroform-d)δ:164.1,146.8,144.9,138.7,133.0,129.41,129.40,129.3,1 29.1,128.15,128.14,128.13,127.34,127.33,127.28,127.27,117.8,117.5,114.5,76.8;

[0070] 2,2,4-Triphenyl-1,2-dihydroquinazoline is a yellow solid with a yield of 75%, mp = 173–174 °C, HRMS calculation for C 26 H 21 N2 + 361.1699, found 361.1702[M+H] + .

[0071] Example 2

[0072] Synthesis of 2,2-diphenyl-4-(p-tolyl)-1,2-dihydroquinazoline (I-2)

[0073]

[0074] The ketimine compound (N-(4-methylbenzyl)-1,1-diphenylmethanimine), the o-iodoaniline compound (2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, and potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C. The mixture was sealed under a nitrogen atmosphere and stirred at 100°C for 12 hours. The reaction was quenched by adding water and diluted with ethyl acetate, and then filtered on a 2 cm thick silica gel pad and washed with ethyl acetate for 3 times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 2,2-diphenyl-4-(p-tolyl)-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline compound and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio was 30:1).

[0075] NMR of 2,2-diphenyl-4-(p-tolyl)-1,2-dihydroquinazoline: 1 HNMR (600 MHz, Chloroform-d) δ 7.49 (t, J = 7.9 Hz, 6H), 7.34-7.17 (m, 9H), 7.07 (d, J = 7.8 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.60 (t, J = 7.5 Hz, 1H), 4.65 (s, 1H), 2.39 (s, 3H) ppm;

[0076] NMR of 2,2-diphenyl-4-(p-tolyl)-1,2-dihydroquinazoline: 13 C{ 1 H}NMR (150 MHz, Chloroform-d) δ 164.0, 146.8, 144.9, 139.3, 135.9, 132.90, 132.89, 129.41, 129.40, 129.1, 128.81, 128.80, 128.10, 128.09, 127.29, 127.27, 117.8, 117.7, 114.5, 76.7, 21.5;

[0077] 2,2-diphenyl-4-(p-tolyl)-1,2-dihydroquinazoline was a yellow solid with a yield of 79%, m.p. = 181-182°C, HRMS (ESI+) [M+H] + calc'd for C 27 H 23 N2 +: 375.1856, found: 375.1858.

[0078] Example 3

[0079] Synthesis of 4-(4-methoxyphenyl)-2,2-diphenyl-1,2-dihydroquinazoline (I-3)

[0080]

[0081] The ketimine compound (N-(4-methoxybenzyl)-1,1-diphenylmethanimine), the o-iodoaniline compound (2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C, and the reaction was carried out under a nitrogen atmosphere at 100°C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction filtered on a 2 cm thick silica gel pad, and the reaction bottle and silica gel pad were washed with ethyl acetate for 3 times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 4-(4-methoxyphenyl)-2,2-diphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline and potassium bis(trimethylsilyl)amide was 2:1:3, the amount ratio of 2-iodoaniline and anhydrous 1,4-dioxane was 1 g:40 mL, the amount ratio of the o-iodoaniline compound and the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio was 30:1).

[0082] NMR of 4-(4-methoxyphenyl)-2,2-diphenyl-1,2-dihydroquinazoline: 1 HNMR (600 MHz, Chloroform-d) δ 7.53 (dd, J = 39.2, 8.1 Hz, 6H), 7.24 (dt, J = 33.1, 7.2 Hz, 7H), 7.09 (d, J = 7.8 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 6.74 (d, J = 8.0 Hz, 1H), 6.61 (t, J = 7.5 Hz, 1H), 4.67 (s, 1H), 3.82 (s, 3H);

[0083] NMR of 4-(4-methoxyphenyl)-2,2-diphenyl-1,2-dihydroquinazoline: 13 C{ 1H}NMR (150 MHz, Chloroform-d) δ 163.5, 160.6, 146.8, 145.0, 132.9, 131.2, 131.01, 131.02, 129.0, 128.10, 128.11, 127.31, 127.30, 127.29, 117.7, 117.7, 114.6, 113.51, 113.50, 76.6, 55.5;

[0084] 4-(4-methoxyphenyl)-2,2-diphenyl-1,2-dihydroquinazoline was obtained as a yellow solid in 84% yield, m.p. = 141-142 °C, HRMS (ESI + [M+H] + calc'd for C 27 H 23 N2O + : 391.1805, found: 391.1802.

[0085] Example 4

[0086] Synthesis of 2,2-diphenyl-4-(o-tolyl)-1,2-dihydroquinazoline (I-4)

[0087]

[0088] The ketimine compound (N-(2-methylbenzyl)-1,1-diphenylmethanimine), the o-iodoaniline compound (2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100 °C, and the mixture was sealed under a nitrogen atmosphere and reacted at 100 °C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction-filtered over a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three more times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 2,2-diphenyl-4-(o-tolyl)-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline, and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the eluent for column chromatography was petroleum ether-ethyl acetate (volume ratio of 30:1).

[0089] NMR spectrum of 2,2-diphenyl-4-(o-tolyl)-1,2-dihydroquinazoline: 1HNMR (600 MHz, Chloroform-d) δ 7.49 (d, J = 7.7 Hz, 4H), 7.35 - 7.13 (m, 11H), 6.66 (dd, J = 13.9, 7.9 Hz, 2H), 6.51 (d, J = 7.5 Hz, 1H), 4.58 (s, 1H), 2.02 (s, 3H);

[0090] NMR Carbon Spectrum of 2,2-Diphenyl-4-(o-tolyl)-1,2-dihydroquinazoline: 13 C{ 1 H}NMR (150 MHz, Chloroform-d) δ 165.1, 146.7, 143.9, 138.4, 136.10, 136.09, 133.4, 130.32, 130.31, 128.7, 128.5, 128.3, 128.12, 128.11, 127.4, 127.31, 127.30, 125.8, 117.9, 117.5, 113.9, 77.2, 19.4;

[0091] 2,2-Diphenyl-4-(o-tolyl)-1,2-dihydroquinazoline was obtained as a yellow solid in 77% yield, m.p. = 169-170 °C. HRMS (ESI) [M+H] calcd for C + [M+H] + calc'd for C 27 H 23 N2 + : 375.1856, found: 375.1857.

[0092] Example 5

[0093] Synthesis of 4-(4-Fluorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline (I-5)

[0094]

[0095] In a nitrogen atmosphere, ketoimine compounds (N-(4-fluorobenzyl)-1,1-diphenylmethylimine) and o-iodoaniline compounds (2-iodoaniline) were dissolved in anhydrous 1,4-dioxane. At 100°C, potassium bis(trimethylsilyl)amino was added and mixed thoroughly. The mixture was sealed in a nitrogen atmosphere and reacted at 100°C with stirring for 12 hours. The reaction was quenched with water, diluted with ethyl acetate, and then filtered through a 2 cm thick silica gel pad. The reaction flask and silica gel pad were rinsed three times with ethyl acetate. All the filtered material was then filtered through a vacuum filter. The crude product was concentrated under reduced pressure and separated by column chromatography using deactivated silica gel to obtain 4-(4-fluorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline. The molar ratio of the ketoimine compound, o-iodoaniline, and potassium bis(trimethylsilyl)amino was 2:1:3; the volume ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL; the volume ratio of o-iodoaniline compounds to ethyl acetate for dilution was 0.2 mmol:3 mL; and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio 30:1).

[0096] 1H NMR spectrum of 4-(4-fluorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline: 1 HNMR(600MHz,Chloroform-d)δ7.57(dd,J=8.4,5.5Hz,2H),7.48(d,J=7.8Hz,4H),7.30-7.18(m,7H),7 .08(t,J=8.6Hz,2H),7.00(d,J=7.8Hz,1H),6.72(d,J=8.1Hz,1H),6.59(t,J=7.5Hz,1H),4.65(s,1H);

[0097] Carbon NMR spectrum of 4-(4-fluorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline: 13 C{ 1 H}NMR(150MHz,Chloroform-d)δ163.6(d, 1 J C-F =247.5Hz),163.1,146.57,146.56,144.9,134.7(d, 4 J C-F =3.0Hz), 133.2, 131.4(d, 3 J C-F =9.0Hz),128.8,128.15,128.14,127.38,127.37,127.21,127.20,117.8,117.3,115.1(d, 2 J C-F =21.0Hz), 114.6, 76.8;

[0098] 4-(4-Fluorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline was obtained as a yellow solid in 68% yield, m.p. = 180-181 °C, HRMS (ESI) [M+H] calcd for C + [M+H] + calcd for C 26 H 20 FN2 + : 379.1605, found: 379.1602.

[0099] Example 6

[0100] Synthesis of 4-(4-Chlorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline (I-6)

[0101]

[0102] The ketimine compound (N-(4-chlorobenzyl)-1,1-diphenylmethanimine), the o-iodoaniline compound (2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100 °C, and the mixture was sealed under a nitrogen atmosphere and stirred at 100 °C for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then filtered on a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 4-(4-chlorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the eluent for column chromatography was petroleum ether-ethyl acetate (volume ratio of 30:1).

[0103] NMR of 4-(4-Chlorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline: 1 HNMR (400 MHz, Chloroform-d) δ 7.62-7.44 (m, 6H), 7.44-7.36 (m, 2H), 7.34-7.17 (m, 7H), 6.99 (dd, J = 7.8, 1.4 Hz, 1H), 6.74 (dd, J = 8.1, 1.1 Hz, 1H), 6.60 (td, J = 7.6, 1.1 Hz, 1H), 4.65 (s, 1H);

[0104] 4-(4-chlorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline: 13 C{ 1 H}NMR (100 MHz, Chloroform-d) δ 163.1, 146.5, 144.9, 137.0, 135.4, 133.3, 130.84, 130.83, 128.7, 128.40, 128.39, 128.18, 128.17, 127.4, 127.20, 127.19, 117.9, 117.1, 114.6, 76.8;

[0105] 4-(4-chlorophenyl)-2,2-diphenyl-1,2-dihydroquinazoline was obtained as a yellow solid in 57% yield, m.p. = 178-179 °C, HRMS (ESI + )[M+H] + calc'd for C 26 H 20 ClN2 + :395.1310, found:395.1312.

[0106] Example 7

[0107] Synthesis of 4-(naphthalen-2-yl)-2,2-diphenyl-1,2-dihydroquinazoline (I-7)

[0108]

[0109] The ketimine compound (N-(naphthalen-2-ylmethyl)-1,1-diphenylmethanimine), the o-iodoaniline compound (2-iodoaniline) and potassium bis(trimethylsilyl)amide were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, mixed uniformly at 100 °C, sealed under a nitrogen atmosphere, reacted under stirring at 100 °C for 12 h, quenched by adding water, diluted with ethyl acetate, then subjected to suction filtration on a 2 cm thick silica gel pad, and the reaction bottle and silica gel pad were washed with ethyl acetate for 3 times, and all the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 4-(naphthalen-2-yl)-2,2-diphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio was 30:1).

[0110] NMR (400 MHz, Chloroform-d) δ 8.22 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.87 (d, J = 8.0 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.68 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 6.64 (d, J = 8.0 Hz, 1H), 6.62 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.0 Hz, 1H), 6.58 (d, J = 8.0 Hz, 1H), 6.56 (d, J = 8.0 Hz, 1H), 6.54 (d, J = 8.0 Hz, 1H), 6.52 (d, J = 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 6.48 (d, J = 8.0 Hz, 1H), 6.46 (d, J = 8.0 Hz, 1H), 6.44 (d, J = 8.0 Hz, 1H), 6.42 (d, J = 8.0 Hz, 1H), 6.40 (d, J = 8.0 Hz, 1H), 6.38 (d, J = 8.0 Hz, 1H), 6.36 (d, J = 8.0 Hz, 1H), 6.34 (d, J = 8.0 Hz, 1H), 6.32 (d, J = 8.0 Hz, 1H), 6.30 (d, J = 8.0 Hz, 1H), 6.28 (d, J = 8.0 Hz, 1H), 6.26 (d, J = 8.0 Hz, 1H), 6.24 (d, J = 8.0 Hz, 1H), 6.22 (d, J = 8.0 Hz, 1H), 6.20 (d, J = 8.0 Hz, 1H), 6.18 (d, J = 8.0 Hz, 1H), 6.16 (d, J = 8.0 Hz, 1H), 6.14 (d, J = 8.0 Hz, 1H), 6.12 (d, J = 8.0 Hz, 1H), 6.10 (d, J = 8.0 Hz, 1H), 6.08 (1 H NMR (600 MHz, Chloroform-d) δ 8.05 (s, 1H), 7.87 (td, J = 9.2, 8.8, 5.6 Hz, 3H), 7.72 (dd, J = 8.5, 1.6 Hz, 1H), 7.60 - 7.46 (m, 6H), 7.34 - 7.18 (m, 7H), 7.10 (d, J = 7.8 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 6.61 (t, J = 7.5 Hz, 1H), 4.69 (s, 1H);

[0111] NMR Carbon Spectrum of 4-(Naphthalen-2-yl)-2,2-diphenyl-1,2-dihydroquinazoline: 13 C{ 1 H} NMR (150 MHz, Chloroform-d) δ 164.1, 146.7, 145.0, 136.1, 133.9, 133.11, 133.10, 133.0, 129.1, 129.0, 128.7, 128.18, 128.16, 127.84, 127.83, 127.40, 127.39, 127.31, 127.30, 127.1, 126.7, 126.3, 117.9, 117.7, 114.6, 76.9;

[0112] 4-(Naphthalen-2-yl)-2,2-diphenyl-1,2-dihydroquinazoline was obtained as a yellow solid in 69% yield, m.p. = 181-182 °C, HRMS (ESI + )[M+H] + calc'd for C 30 H 23 N2 + : 411.1856, found: 411.1857.

[0113] Example 8

[0114] Synthesis of 2,2-Diphenyl-4-(pyridin-3-yl)-1,2-dihydroquinazoline (I-8)

[0115]

[0116] The ketimine compound (1,1-diphenyl-N-(pyridin-3-ylmethyl)methanimine), the o-iodoaniline compound (2-iodoaniline) are dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, and potassium bis(trimethylsilyl)amide is added and mixed uniformly at 100°C. The reaction is carried out under a nitrogen atmosphere at 100°C with stirring for 12 h, and the reaction is quenched by adding water and diluted with ethyl acetate, followed by suction filtration on a 2 cm thick silica gel pad, and the reaction flask and silica gel pad are washed with ethyl acetate for 3 times. All the filtrate is concentrated under reduced pressure, and the crude product is separated by column chromatography on deactivated silica gel to obtain 2,2-diphenyl-4-(pyridin-3-yl)-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline and potassium bis(trimethylsilyl)amide is 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane is 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate is 0.2 mmol:3 mL, and the column chromatography eluent is petroleum ether-ethyl acetate (volume ratio is 10:1).

[0117] Nuclear magnetic resonance hydrogen spectrum of 2,2-diphenyl-4-(pyridin-3-yl)-1,2-dihydroquinazoline: 1 HNMR (400 MHz, Chloroform-d) δ 8.84 (s, 1H), 8.67 (d, J = 4.9 Hz, 1H), 7.91 (dt, J = 7.9, 1.9 Hz, 1H), 7.50 (d, J = 7.5 Hz, 4H), 7.40-7.21 (m, 8H), 7.00 (d, J = 7.8 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 6.64 (t, J = 7.6 Hz, 1H), 4.76 (s, 1H);

[0118] Nuclear magnetic resonance carbon spectrum of 2,2-diphenyl-4-(pyridin-3-yl)-1,2-dihydroquinazoline: 13 C{ 1 H}NMR (100 MHz, Chloroform-d) δ 161.7, 150.4, 150.3, 146.40, 146.38, 144.9, 137.0, 134.3, 133.6, 128.5, 128.25, 128.24, 127.52, 127.51, 127.17, 127.16, 123.1, 118.1, 117.0, 114.7, 76.9;

[0119] 2,2-diphenyl-4-(pyridin-3-yl)-1,2-dihydroquinazoline is a yellow solid with a yield of 42%, m.p. = 226-227°C, HRMS (ESI + )[M+H] +Calc'd for C 25 H 20 N3 + : 362.1652, Found: 362.1657.

[0120] Example 9

[0121] Synthesis of 2,2-diphenyl-4-(thiophen-2-yl)-1,2-dihydroquinazoline (I-9)

[0122]

[0123] The ketimine compound (1,1-diphenyl-N-(thiophen-2-ylmethyl)methanimine), the o-iodoaniline compound (2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C, and the mixture was sealed under a nitrogen atmosphere and reacted at 100°C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction-filtered over a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 2,2-diphenyl-4-(thiophen-2-yl)-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline, and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio of 30:1).

[0124] NMR of 2,2-diphenyl-4-(thiophen-2-yl)-1,2-dihydroquinazoline: 1 HNMR (400 MHz, Chloroform-d) δ 7.50 (dd, J = 8.3, 1.5 Hz, 5H), 7.47-7.40 (m, 2H), 7.30-7.23 (m, 5H), 7.23-7.17 (m, 2H), 7.09 (dd, J = 5.1, 3.6 Hz, 1H), 6.80 (dd, J = 8.1, 1.1 Hz, 1H), 6.71 (td, J = 7.6, 1.1 Hz, 1H), 4.71 (s, 1H);

[0125] NMR of 2,2-diphenyl-4-(thiophen-2-yl)-1,2-dihydroquinazoline: 13 C{ 1H}NMR (100 MHz, Chloroform-d) δ 157.4, 146.4, 145.16, 145.15, 133.1, 129.2, 128.5, 128.2, 128.15, 128.12, 127.34, 127.33, 127.22, 127.20, 127.18, 127.17, 118.2, 117.5, 115.1, 76.3;

[0126] 2,2-diphenyl-4-(thiophen-2-yl)-1,2-dihydroquinazoline was obtained as a yellow solid in 51% yield, m.p. = 198-199°C, HRMS (ESI + [M+H] + calc'd for C 24 H 19 N2S + : 367.1263, found: 367.1264.

[0127] Example 10

[0128] Synthesis of 6-methyl-2,2,4-triphenyl-1,2-dihydroquinazoline (I-10)

[0129]

[0130] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (2-iodo-4-methylaniline) and potassium bis(trimethylsilyl)amide were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, mixed uniformly at 100°C, sealed under a nitrogen atmosphere, and reacted at 100°C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction-filtered over a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three more times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 6-methyl-2,2,4-triphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline, and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0131] NMR of 6-methyl-2,2,4-triphenyl-1,2-dihydroquinazoline: 1H NMR (400 MHz, Chloroform-d) δ 7.64 - 7.37 (m, 9 H), 7.34 - 7.16 (m, 6 H), 7.07 (dd, J = 8.2, 2.0 Hz, 1 H), 6.84 (s, 1 H), 6.68 (d, J = 8.1 Hz, 1 H), 4.55 (s, 1 H), 2.12 (s, 3 H);

[0132] 6-Methyl-2,2,4-triphenyl-1,2-dihydroquinazoline Carbon NMR spectrum: 13 C{ 1 H} NMR (100 MHz, Chloroform-d) δ 164.2, 146.7, 142.68, 142.67, 138.7, 133.9, 129.43, 129.3, 129.1, 128.15, 128.14, 128.11, 128.10, 127.31, 127.30, 127.29, 127.1, 117.7, 114.7, 76.7, 20.7;

[0133] 6-Methyl-2,2,4-triphenyl-1,2-dihydroquinazoline was obtained as a yellow solid in 78% yield, m.p. = 201 -202 °C, HRMS (ESI + )[M+H] + calc'd for C 27 H 23 N2 + : 375.1856, found: 375.1855.

[0134] Example 11

[0135] Synthesis of 6-(tert-butyl)-2,2,4-triphenyl-1,2-dihydroquinazoline (1-11)

[0136]

[0137] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (4-(tert-butyl)-2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, and potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C. The reaction was carried out under a nitrogen atmosphere at 100°C with stirring for 12 hours, and then the reaction was quenched by adding water and diluted with ethyl acetate. The reaction vessel and silica gel pad were then washed with ethyl acetate for 3 times, and all the filtrate was concentrated under reduced pressure. The crude product was separated by column chromatography using deactivated silica gel to obtain 6-(tert-butyl)-2,2,4-triphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline, and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL. The eluent for column chromatography was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0138] NMR of 6-(tert-butyl)-2,2,4-triphenyl-1,2-dihydroquinazoline: 1 HNMR (400 MHz, Chloroform-d) δ 7.65-7.57 (m, 2H), 7.55-7.48 (m, 4H), 7.45-7.38 (m, 3H), 7.33-7.24 (m, 5H), 7.18-7.22 (m, 2H), 7.08 (d, J = 2.3 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 4.52 (s, 1H), 1.16 (s, 9H);

[0139] NMR of 6-(tert-butyl)-2,2,4-triphenyl-1,2-dihydroquinazoline: 13 C{ 1 H}NMR (100 MHz, Chloroform-d) δ 164.3, 147.01, 147.00, 142.5, 140.5, 138.8, 130.3, 129.5, 129.3, 128.10, 128.09, 128.09, 128.07, 127.31, 127.30, 127.2, 125.8, 117.0, 114.2, 76.7, 34.1, 31.4;

[0140] 6-(tert-butyl)-2,2,4-triphenyl-1,2-dihydroquinazoline was a yellow solid with a yield of 74% and m.p. = 206-207°C. HRMS (ESI + )[M+H] + calc'd for C 30 H29 N2 + :427.2325, found:427.2330.

[0141] Example 12

[0142] Synthesis of 8-methoxy-2,2,4-triphenyl-1,2-dihydroquinazoline (I-12)

[0143]

[0144] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (2-iodo-6-methoxyaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C, and the mixture was sealed under a nitrogen atmosphere and reacted at 100°C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then filtered on a 2 cm thick silica gel pad, and the reaction bottle and silica gel pad were washed with ethyl acetate three times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 8-methoxy-2,2,4-triphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0145] NMR spectrum of 8-methoxy-2,2,4-triphenyl-1,2-dihydroquinazoline: 1 H NMR (400 MHz, Chloroform-d) δ 7.69 (dd, J = 6.6, 3.1 Hz, 2H), 7.61-7.55 (m, 4H), 7.52-7.45 (m, 3H), 7.40-7.34 (m, 4H), 7.33-7.28 (m, 2H), 6.91 (dd, J = 8.0, 1.2 Hz, 1H), 6.75-6.78 (m, 1H), 6.62 (t, J = 8.0 Hz, 1H), 5.31 (s, 1H), 3.97 (s, 3H);

[0146] NMR spectrum of 8-methoxy-2,2,4-triphenyl-1,2-dihydroquinazoline: 13 C{ 1H}NMR (100 MHz, Chloroform-d) δ 163.0, 145.7, 144.96, 144.95, 137.8, 134.5, 128.38, 128.37, 128.2, 127.09, 127.08, 127.07, 126.3, 126.16, 126.15, 119.8, 115.9, 115.2, 111.6, 75.7, 54.8;

[0147] 8-methoxy-2,2,4-triphenyl-1,2-dihydroquinazoline as a yellow solid in 82% yield, m.p. = 182-183 °C, HRMS (ESI + [M+H] + calc'd for C 27 H 23 N2O + : 391.1805, found: 391.1806.

[0148] Example 13

[0149] Synthesis of 7-fluoro-2,2,4-triphenyl-1,2-dihydroquinazoline (I-13)

[0150]

[0151] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (5-fluoro-2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100 °C, and the mixture was sealed under a nitrogen atmosphere and reacted at 100 °C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction-filtered over a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three more times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 7-fluoro-2,2,4-triphenyl-1,2-dihydroquinazoline. The molar ratio of the ketimine compound, the o-iodoaniline, and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL. The eluent for column chromatography was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0152] NMR of 7-fluoro-2,2,4-triphenyl-1,2-dihydroquinazoline: 1H NMR (400 MHz, Chloroform-d) δ 7.60 - 7.37 (m, 9 H), 7.37 - 7.20 (m, 6 H), 7.03 (dd, J = 8.7, 6.2 Hz, 1 H), 6.44 (dd, J = 9.9, 2.4 Hz, 1 H), 6.27 - 6.32 (m, 1 H), 4.79 (s, 1 H);

[0153] 7-Fluoro-2,2,4-triphenyl-1,2-dihydroquinazoline Carbon NMR: 13 C{ 1 H} NMR (100 MHz, Chloroform-d) δ 166.0 (d, 1 J C-F = 250.0 Hz), 163.3, 146.8 (d, 3 J C-F = 12.0 Hz), 146.37, 146.36, 138.4, 131.6, 131.4, 129.5, 129.3, 128.26, 128.25, 128.24, 127.5, 127.21, 127.20, 114.0 (d, 4 J C-F = 2.0 Hz), 105.2 (d, 2 J C-F = 22.0 Hz), 100.8 (d, 2 J C-F = 25.0 Hz), 77.0;

[0154] 7-Fluoro-2,2,4-triphenyl-1,2-dihydroquinazoline was obtained as a yellow solid in 67% yield, m.p. = 181 -182 °C, HRMS (ESI + )[M+H] + calc'd for C 26 H 19 FN2 + : 379.1605, found: 379.1601.

[0155] Example 14

[0156] Synthesis of 6-Chloro-2,2,4-triphenyl-1,2-dihydroquinazoline (1-14)

[0157]

[0158] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (4-chloro-2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, and potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C. The mixture was sealed under a nitrogen atmosphere and reacted at 100°C with stirring for 12 hours. The reaction was quenched by adding water and diluted with ethyl acetate, and then filtered on a 2 cm thick silica gel pad and washed with ethyl acetate for 3 times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 6-chloro-2,2,4-triphenyl-1,2-dihydroquinazoline. The molar ratio of the ketimine compound, the o-iodoaniline compound, and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL. The eluent for column chromatography was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0159] NMR spectrum of 6-chloro-2,2,4-triphenyl-1,2-dihydroquinazoline: 1 H NMR (400 MHz, Chloroform-d) δ 7.60-7.55 (m, 2H), 7.51-7.43 (m, 7H), 7.30 (dd, J = 8.3, 6.4 Hz, 4H), 7.26-7.18 (m, 3H), 7.04 (d, J = 2.3 Hz, 1H), 6.72 (d, J = 8.5 Hz, 1H), 4.69 (s, 1H);

[0160] NMR spectrum of 6-chloro-2,2,4-triphenyl-1,2-dihydroquinazoline: 13 C{ 1 H} NMR (100 MHz, Chloroform-d) δ 163.1, 146.2, 143.45, 143.44, 137.9, 133.0, 129.7, 129.3, 128.6, 128.40, 128.39, 128.26, 128.25, 127.6, 127.20, 27.19, 122.5, 118.4, 115.9, 77.0;

[0161] 6-chloro-2,2,4-triphenyl-1,2-dihydroquinazoline was a yellow solid with a yield of 64% and m.p. = 217-218°C. HRMS (ESI + )[M+H] + calc'd for C 26 H 20 ClN2 +: 395.1310, found: 395.1309.

[0162] Example 15

[0163] Synthesis of 6-bromo-2,2,4-triphenyl-1,2-dihydroquinazoline (I-15)

[0164]

[0165] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (4-bromo-2-iodoaniline) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C, and the reaction was carried out under a nitrogen atmosphere at 100°C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction filtered on a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate for 3 times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 6-bromo-2,2,4-triphenyl-1,2-dihydroquinazoline; wherein the molar ratio of the ketimine compound, the o-iodoaniline and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio was 15:1).

[0166] NMR spectrum of 6-bromo-2,2,4-triphenyl-1,2-dihydroquinazoline: 1 H NMR (400 MHz, Chloroform-d) δ 7.58 (dd, J = 6.6, 2.9 Hz, 2H), 7.51 (dd, J = 7.4, 1.7 Hz, 4H), 7.42 (dd, J = 5.0, 1.9 Hz, 3H), 7.30 (d, J = 7.3 Hz, 3H), 7.27-7.19 (m, 3H), 7.08-6.99 (m, 1H), 6.75 (d, J = 8.0 Hz, 1H), 6.61 (t, J = 7.5 Hz, 1H), 4.66 (s, 1H);

[0167] NMR spectrum of 6-bromo-2,2,4-triphenyl-1,2-dihydroquinazoline: 13 C{ 1H}NMR (100 MHz, Chloroform-d) δ 164.1, 146.71, 146.70, 144.9, 138.6, 133.1, 129.42, 129.41, 129.3, 129.1, 128.15, 128.14, 128.13, 127.4, 127.28, 127.27, 117.8, 117.5, 114.5, 76.8;

[0168] 6-bromo-2,2,4-triphenyl-1,2-dihydroquinazoline as a yellow solid in 60% yield, m.p. = 177-178 °C, HRMS (ESI + [M+H] + calc'd for C 26 H 20 BrN2 + : 439.0804, found: 439.0803.

[0169] Example 16

[0170] Synthesis of 1,3,3-triphenyl-3,4-dihydrobenzoquinazoline (I-16)

[0171]

[0172] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (1-iodonaphthalen-2-amine) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100 °C, and the mixture was reacted under stirring at 100 °C for 12 h under a nitrogen atmosphere. The reaction was quenched by adding water, diluted with ethyl acetate, and then filtered on a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 1,3,3-triphenyl-3,4-dihydrobenzoquinazoline. The molar ratio of the ketimine compound, the o-iodoaniline, and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL. The eluent for column chromatography was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0173] NMR of 1,3,3-triphenyl-3,4-dihydrobenzoquinazoline: 1H NMR (400 MHz, Chloroform-d) δ 7.77 (d, J = 8.8 Hz, 1H), 7.65 - 7.52 (m, 5H), 7.46 - 7.37 (m, 3H), 7.34 (dd, J = 8.0, 6.4 Hz, 2H), 7.24 (dd, J = 6.2, 1.7 Hz, 4H), 7.21 - 7.15 (m, 2H), 7.12 - 7.05 (m, 2H), 6.92 - 6.96 (m, 1H), 6.82 (d, J = 8.5 Hz, 1H), 5.08 (s, 1H);

[0174] 1,3,3- Triphenyl- 3,4-dihydrobenzoquinazoline Carbon NMR Spectrum: 13 C{ 1 H} NMR (100 MHz, Chloroform-d) δ 164.1, 145.9, 144.61, 144.60, 141.8, 134.3, 131.1, 129.4, 129.1, 128.5, 128.5, 128.3, 128.12, 128.11, 127.31, 127.30, 127.29, 127.3, 126.7, 126.0, 122.6, 117.0, 112.3, 75.8;

[0175] 1,3,3- Triphenyl- 3,4-dihydrobenzoquinazoline was obtained as a yellow solid in 56% yield, m.p. = 225-226 °C, HRMS (ESI + )[M+H] + calc'd for C 30 H 23 N2 + : 411.1856, found: 411.1851.

[0176] Example 17

[0177] Synthesis of 2,2,4-triphenyl- 1,2-dihydropyrido[3,4-d]pyrimidine (1-17)

[0178]

[0179] The ketimine compound (N-benzyl-1,1-diphenylmethanimine), the o-iodoaniline compound (4-iodopyridin-3-amine) were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, and potassium bis(trimethylsilyl)amide was added and mixed uniformly at 100°C. The mixture was sealed under a nitrogen atmosphere and stirred at 100°C for 12 hours. The reaction was quenched by adding water and diluted with ethyl acetate, and then filtered on a 2 cm thick silica gel pad and washed with ethyl acetate for 3 times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 2,2,4-triphenyl-1,2-dihydropyrido[3,4-d]pyrimidine. The molar ratio of the ketimine compound, the o-iodoaniline and potassium bis(trimethylsilyl)amide was 2:1:3, the ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL. The eluent for column chromatography was petroleum ether-ethyl acetate (10:1 by volume).

[0180] NMR of 2,2,4-triphenyl-1,2-dihydropyrido[3,4-d]pyrimidine: 1 HNMR (400 MHz, Chloroform-d) δ 8.29 (s, 1H), 7.95 (d, J = 5.1 Hz, 1H), 7.65-7.55 (m, 2H), 7.54-7.41 (m, 7H), 7.35-7.28 (m, 4H), 7.28-7.24 (m, 2H), 6.94 (d, J = 5.1 Hz, 1H), 4.82 (s, 1H);

[0181] NMR of 2,2,4-triphenyl-1,2-dihydropyrido[3,4-d]pyrimidine: 13 C{ 1 H}NMR (100 MHz, Chloroform-d) δ 162.4, 146.01, 146.00, 140.2, 139.3, 138.96, 138.95, 137.2, 130.0, 129.2, 128.5, 128.38, 128.37, 127.7, 127.13, 127.12, 121.9, 120.9, 77.0;

[0182] 2,2,4-triphenyl-1,2-dihydropyrido[3,4-d]pyrimidine was a yellow solid with a yield of 45% and m.p. = 269-270°C. HRMS (ESI + )[M+H] + calc'd for C 25 H 20 N3 +:362.1652.

[0183] Example 18

[0184] Synthesis of 4'-phenyl-1'H-spiro[fluorene-9,2'-quinazoline] (II-1)

[0185]

[0186] The aldimine compound (N-(9H-fluoren-9-yl)-1-phenylmethanimine), the o-iodoaniline compound (2-iodoaniline) and potassium tert-butoxide were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, mixed uniformly at 100°C, sealed under a nitrogen atmosphere, and reacted at 100°C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction-filtered over a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three more times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography using deactivated silica gel to obtain 4'-phenyl-1'H-spiro[fluorene-9,2'-quinazoline]. The molar ratio of N-(9H-fluoren-9-yl)-1-phenylmethanimine, 2-iodoaniline and potassium tert-butoxide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the amount of ethyl acetate used for dilution was 0.2 mmol:3 mL. The eluent for column chromatography was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0187] NMR spectrum of 4'-phenyl-1'H-spiro[fluorene-9,2'-quinazoline] (II-1): 1 H NMR (600 MHz, Chloroform-d) δ: 7.64 (d, J = 7.6 Hz, 2H), 7.61-7.51 (m, 4H), 7.45-7.32 (m, 5H), 7.24-7.18 (m, 4H), 6.73 (t, J = 7.6 Hz, 1H), 6.54 (d, J = 8.2 Hz, 1H), 4.37 (s, 1H);

[0188] NMR spectrum of 4'-phenyl-1'H-spiro[fluorene-9,2'-quinazoline] (II-1): 13 C NMR (150 MHz, Chloroform-d) δ: 166.5, 149.66, 149.65, 146.4, 138.68, 138.67, 138.4, 132.94, 132.93, 129.8, 129.3, 129.16, 129.15, 128.8, 128.5, 128.27, 128.26, 124.74, 124.73, 120.2, 118.2, 117.1, 114.6, 80.7;

[0189] 4'-phenyl-1 'H-spiro[fluorene-9,2'-quinazoline] is a yellow solid with a yield of 72% and m.p. = 182-183 °C. HRMS calc'd for C 26 H 19 N2 + : 359.1543, found: 359.1539.

[0190] Example 19

[0191] Synthesis of 4'-cyclopropyl-1 'H-spiro[fluorene-9,2'-quinazoline] (II-2)

[0192]

[0193] The aldimine compound (1-isopropyl-N-(9H-fluoren-9-yl)methanimine), the o-iodoaniline compound (2-iodoaniline) and potassium tert-butoxide were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, mixed uniformly at 100 °C, sealed under a nitrogen atmosphere, and reacted at 100 °C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then suction-filtered over a 2 cm thick silica gel pad, and the reaction flask and silica gel pad were washed with ethyl acetate three more times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 4'-cyclopropyl-1 'H-spiro[fluorene-9,2'-quinazoline]; wherein the molar ratio of the aldimine compound, the o-iodoaniline, and potassium tert-butoxide was 2:1:3, the amount ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the amount ratio of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio of 15:1).

[0194] The nuclear magnetic resonance hydrogen spectrum of 4'-cyclopropyl-1 'H-spiro[fluorene-9,2'-quinazoline]: 1 H NMR (400 MHz, Chloroform-d) δ: 7.70 (dd, J = 7.8, 1.4 Hz, 1H), 7.58 (d, J = 7.5 Hz, 2H), 7.42 (d, J = 7.5 Hz, 2H), 7.33 (td, J = 7.5, 1.2 Hz, 2H), 7.15-7.19 (m, 3H), 6.79 (td, J = 7.6, 1.1 Hz, 1H), 6.41 (dd, J = 8.0, 1.1 Hz, 1H), 4.17 (s, 1H), 2.15-2.22 (m, 1H), 0.91-0.95 (m, 2H), 0.79-0.84 (m, 2H);

[0195] 4'-Cyclopropyl-1 'H-spiro[fluorene-9,2'-quinazoline] NMR Carbon Spectrum: 13 C NMR (100 MHz, Chloroform-d) δ: 166.3, 150.10, 150.09, 145.02, 145.01, 138.4, 132.4, 129.49, 129.48, 128.36, 128.35, 125.7, 124.51, 124.50, 120.04, 120.03, 118.2, 117.8, 114.2, 80.1, 14.0, 7.6;

[0196] 4'-Cyclopropyl-1 'H-spiro[fluorene-9,2'-quinazoline] was a yellow solid with a yield of 82% and m.p. = 209-210 °C. HRMS calc'd for C 23 H 19 N2 + 323.1543, found 323.1545 [M+H] + .

[0197] Example 20

[0198] Synthesis of 4'-Cyclohexyl-1 'H-spiro[fluorene-9,2'-quinazoline] (II-3)

[0199]

[0200] The aldimine compound (1-cyclohexyl-N-(9H-fluoren-9-yl)methanimine), the o-iodoaniline compound (2-iodoaniline) and potassium tert-butoxide were dissolved in anhydrous 1,4-dioxane under a nitrogen atmosphere, mixed uniformly at 100 °C, sealed under a nitrogen atmosphere, reacted under stirring at 100 °C for 12 h, quenched with water, diluted with ethyl acetate, then subjected to suction filtration on a 2 cm thick silica gel pad, the reaction bottle and silica gel pad were washed with ethyl acetate for 3 times, and all the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 4'-cyclohexyl-1 'H-spiro[fluorene-9,2'-quinazoline]; wherein the molar ratio of the aldimine compound, the o-iodoaniline and potassium tert-butoxide was 2:1:3, the amount ratio of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, the amount ratio of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio was 15:1);

[0201] 4'-Cyclohexyl-1 'H-spiro[fluorene-9,2'-quinazoline] NMR Hydrogen Spectrum: 1H NMR (400 MHz, Chloroform-d) δ: 7.60 (d, J = 7.5 Hz, 2H), 7.47 (dd, J = 13.4, 7.6 Hz, 3H), 7.34 (t, J = 7.5 Hz, 2H), 7.24 - 7.13 (m, 3H), 6.76 (t, J = 7.5 Hz, 1H), 6.41 (d, J = 7.9 Hz, 1H), 4.17 (s, 1H), 2.99 - 2.92 (m, 1H), 1.95 - 1.84 (m, 2H), 1.82 - 1.75 (m, 2H), 1.69 - 1.65 (m, 1H), 1.55 - 1.45 (m, 2H), 1.43 - 1.32 (m, 2H), 1.26 - 1.15 (m, 1H);

[0202] 4'-Cyclohexyl-1 'H-spiro[fluorene-9,2'-quinazoline] Carbon NMR Spectrum: 13 C NMR (100 MHz, Chloroform-d) δ: 169.7, 150.2, 145.47, 145.46, 138.40, 138.39, 132.3, 129.42, 129.41, 128.27, 128.26, 125.3, 124.43, 124.42, 120.02, 120.01, 118.1, 116.4, 114.6, 80.1, 41.8, 31.2, 26.6, 26.2;

[0203] 4'-Cyclohexyl-1 'H-spiro[fluorene-9,2'-quinazoline] was obtained as a yellow solid in 53% yield, m.p. = 159-160 °C, HRMS calc'd for C 26 H 25 N2 + 365.2012, found 365.2009. [M+H] + .

[0204] Example 21

[0205] Synthesis of 4'-([1,1'-biphenyl]-4-yl)-1 'H-spiro[fluorene-9,2'-quinazoline] (II-4)

[0206]

[0207] In a nitrogen atmosphere, the aldimine compound (1-([1,1'-biphenyl]-4-yl)-N-(9H-fluoren-9-yl)methanimine), the o-iodoaniline compound (2-iodoaniline) and potassium tert-butoxide were dissolved in anhydrous 1,4-dioxane, mixed uniformly at 100°C, sealed in a nitrogen atmosphere, and reacted at 100°C with stirring for 12 h. The reaction was quenched by adding water, diluted with ethyl acetate, and then filtered on a 2 cm thick silica gel pad, and the reaction bottle and silica gel pad were washed with ethyl acetate three more times. All the filtrate was concentrated under reduced pressure, and the crude product was separated by column chromatography on deactivated silica gel to obtain 4'-([1,1'-biphenyl]-4-yl)-1'H-spiro[fluorene-9,2'-quinazoline]; wherein the molar ratio of the aldimine compound, the o-iodoaniline, and potassium tert-butoxide was 2:1:3, the ratio of the amount of 2-iodoaniline to anhydrous 1,4-dioxane was 1 g:40 mL, and the ratio of the amount of the o-iodoaniline compound to the dilution ethyl acetate was 0.2 mmol:3 mL, and the column chromatography eluent was petroleum ether-ethyl acetate (volume ratio 15:1).

[0208] NMR spectrum of 4'-([1,1'-biphenyl]-4-yl)-1'H-spiro[fluorene-9,2'-quinazoline]: 1 H NMR (400 MHz, Chloroform-d) δ: 7.67-7.57 (m, 9H), 7.45-7.32 (m, 6H), 7.28-7.19 (m, 4H), 6.77 (t, J = 7.6 Hz, 1H), 6.57 (d, J = 8.0 Hz, 1H), 4.39 (s, 1H);

[0209] NMR spectrum of 4'-([1,1'-biphenyl]-4-yl)-1'H-spiro[fluorene-9,2'-quinazoline]: 13 C NMR (100 MHz, Chloroform-d) δ: 166.2, 149.63, 149.62, 146.5, 142.3, 140.9, 138.70, 138.69, 137.3, 133.0, 129.8, 129.71, 129.70, 128.95, 128.94, 128.7, 128.5, 127.7, 127.33, 127.32, 127.05, 127.05, 124.8, 120.2, 118.3, 117.1, 114.7, 80.7;

[0210] 4'-([1,1'-biphenyl]-4-yl)-1'H-spiro[fluorene-9,2'-quinazoline] was a yellow solid with a yield of 76%, m.p. = 270-271°C, and HRMS calc'd for C 32 H 23 N2+ 435.1855, found: 435.1856. [M+H] + .

[0211] The above merely describes the preferred embodiments of the present application, and it should be pointed out that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered as falling within the protection scope of the present application.

Claims

1. A method for preparing a dihydroquinazoline compound, characterized by, The method comprises the following steps: An imine compound, an o-iodoaniline compound, an organic base, and an oxygen-containing organic solvent are mixed, and a series of reduction / radical coupling / S N 2 reaction / oxidation reaction to obtain a dihydroquinazoline compound; The organic base is one or more of potassium bis(trimethylsilyl)amide, potassium tert-butoxide, and sodium bis(trimethylsilyl)amide; The oxygen-containing organic solvent is one or more of 1,4-dioxane, tetrahydrofuran, cyclopentyl methyl ether, methyl tert-butyl ether, and dimethyl sulfoxide; The dihydroquinazoline compound has a structure shown in formula I or formula II: Formula I Formula II; In the formula I, R 1 is hydrogen, methyl, tert-butyl, methoxy or halogen; R 2 is phenyl; R 3 is phenyl; R 4 is phenyl, p-tolyl, p-methoxyphenyl, o-tolyl, p-fluorophenyl, p-chlorophenyl, naphthyl, pyridyl or thienyl; Ar is phenyl, naphthyl or pyridyl; In the formula II, R 5 is phenyl, cyclopropyl, cyclohexyl or [1,1 '-biphenyl]-4-yl; The imine compound is or ; When the imine compound is , the o-iodoaniline compound is , R 1 R 4 is the same as R 1 R 4 in the formula I; When the imine compound is the o-iodoaniline compound is o-iodoaniline, and R 5 is the same as R 5 in Formula II. The series reduction / free radical coupling / S N 2 The temperature of the reaction / oxidation reaction is 95-100°C, and the time is 11-12h.

2. The production method according to claim 1, characterized by, said R 1 is 6-methyl, 6-tert-butyl, 8-methoxy, 6-halo or 7-halo.

3. The production method according to claim 1 or 2, characterized by, The dihydroquinazoline compound has a structure shown in any one of formula I-1 to I-17 and formula II-1 to II-4: I-1 I-2 I-3 I-4 I-5 I-6 I-7 I-8 I-9 I-10 I-11 I-12 I-13 I-14 I-15 I-16 I-17 II-1 II-2 II-3 II-4.

4. The preparation method according to claim 1, characterized in that the molar ratio of the imine compound to the o-iodoaniline compound is 1.5-3:1-1.

5.

5. The preparation method according to claim 1, characterized in that, The molar ratio of the o-iodoaniline compound to the organic base is 1-1.5:2.5-4.

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