Green synthesis method of polycyclic quinazolinone derivative containing ester group

Abstract

The invention provides a green synthesis method of an ester group-containing polycyclic quinazolinone derivative, which comprises the following steps: mixing an N-alkyl olefin quinazolinone compound, a compound with a structure as shown in a formula (II), a photocatalyst and a solvent, and reacting under a blue light irradiation condition to obtain the ester group-containing polycyclic quinazolinone derivative, experiments show that the method provided by the invention is wide in application range of the substrate, the reaction can be carried out without functional group activation on the reaction site of the substrate in the formula (II), the reaction conditions are mild and green, the conversion of the reaction can be completed under the irradiation of blue light, the use amount of the photocatalyst is only about 0.5 mol%, and the catalytic efficiency is high; meanwhile, a specific photocatalyst is selected, so that the yield is increased, and reactants are clean and pollution-free; good application prospects and research values are realized.

Description

Technical Field

[0001] The invention relates to the field of drug synthesis, and in particular to a green synthesis method of polycyclic quinazolinone derivatives containing ester groups. Background Art

[0002] Polycyclic quinazolinone and its derivatives are important skeletons of many natural alkaloids. So far, there are about 200 natural products and commercial drugs containing quinazolinone, especially in polycyclic quinazolinone natural products, compounds containing ester and ketone groups on the C ring of the skeleton often show anti-tumor, anti-viral and anti-bacterial activities, such as: the natural products and drug molecules containing polycyclic quinazolinone skeleton shown in the following structural formula have anti-viral activity, anti-bacterial activity, anti-cancer activity, anti-depressant activity, anti-Alzheimer's disease activity, etc. Therefore, they have received widespread attention from medicinal chemists and chemists.

[0003]

[0004] In addition, polycyclic quinazolinone derivatives containing ester groups can also be used as important chemical building blocks and widely used in functional group transformation, functional material synthesis, drug discovery and other fields. Therefore, it is of great significance to synthesize polycyclic quinazolinone derivatives containing ester structures.

[0005] Traditional methods for constructing polycyclic quinazolinones often require transition metals, such as heavy metal catalysts such as Cu, Ni, and Ru, organotin reagents or equivalent oxidants, resulting in poor atom economy and the generation of toxic waste. In the past few years, the synthesis of polycyclic quinazolinone core skeletons has been mainly based on quinazoline-4-one substrates with N-alkylene side chains, which are prepared by tandem cyclization reactions of free radicals initiated under various conditions. For example, the C(sp) cyclization of alkyl esters was directly induced by di-tert-butyl peroxide (DTBP) or tert-butyl peroxide (TBHP) at 120°C. 3 )-H bond activation, and the polycyclic quinazolinone containing an ester structure is synthesized through a free radical tandem reaction. In addition, since the photochemical reaction has the outstanding characteristics of simple operation, environmental protection and low cost, the photosynthesis method of polycyclic quinazolinone compounds containing an ester structure has attracted much attention. However, the current photochemical synthesis of polycyclic quinazolinone containing an ester structure still faces certain shortcomings. For example: the need to use ultraviolet light, the narrow scope of application of the substrate, the need to add an oxidant, and the use of unstable sulfur ylide substrates.

[0006] Therefore, it is of great significance to improve the adaptability of substrates and develop green and environmentally friendly synthesis methods with mild reaction conditions. Summary of the invention

[0007] In view of this, the technical problem to be solved by the present invention is to provide a green synthesis method for polycyclic quinazolinone derivatives containing ester groups. The method provided by the present invention not only has mild reaction conditions and is environmentally friendly, but also has wide applicability to substrates.

[0008] Compared with the prior art, the present invention provides a green synthesis method for polycyclic quinazolinone derivatives containing ester groups. The method provided by the present invention comprises the steps of mixing an N-alkyl olefin quinazolinone compound, a compound of the structure of formula (II), a photocatalyst and a solvent, and reacting the mixture under the condition of blue light irradiation to obtain a polycyclic quinazolinone derivative containing ester groups. Experiments have shown that the method provided by the present invention has a wide range of application for substrates, the reaction sites of the substrate of formula (II) can react without the need for functional group activation, and the reaction conditions are mild and green. The reaction conversion can be completed under the irradiation of blue light, and the amount of the photocatalyst used is only about 0.5 mol%, with high catalytic efficiency. At the same time, the use of a specific photocatalyst not only improves the yield, but also makes the reactants clean and pollution-free. The method has good application prospects and research value. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 This is the hydrogen spectrum of the compound prepared in Example 1 of the present invention;

[0010] Figure 2 This is the carbon spectrum of the compound prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0011] The present invention provides a green synthesis method of a polycyclic quinazolinone derivative containing an ester group, comprising:

[0012] An N-alkyl olefin quinazolinone compound, a compound of formula (II), a photocatalyst and a solvent are mixed and reacted under blue light irradiation to obtain a polycyclic quinazolinone derivative containing an ester group;

[0013] The N-alkyl olefin quinazolinone compound is of formula (Ia), formula (Ib) or formula (Ic)

[0014]

[0015] Br-CH2CO2R4 formula (II);

[0016] The ester-containing polycyclic quinazolinone derivative is of formula (III-a), formula (III-b) or formula (III-c),

[0017]

[0018]

[0019] in,

[0020] Said n, n' are independently selected from 1, 2 or 3;

[0021] The R and R" are independently selected from hydrogen, C1-C6 alkyl with substituents, C1-C6 alkyl without substituents, C1-C3 alkoxy, halogen, C2-C15 carboxylate or C2-C5 alkoxycarbonyl;

[0022] The R 1 , R 1 '、R 1 " is independently selected from hydrogen or a C1-C3 alkyl group without a substituent;

[0023] The R 2 , R 2 '、R 2 " is independently selected from hydrogen or a C1-C3 alkyl group without a substituent;

[0024] The R 3 , R 3 '、R 3 " is independently selected from hydrogen or a C1-C3 alkyl group without a substituent;

[0025] The R 4 is a C1-C6 alkyl group without a substituent;

[0026] The X is sulfur or oxygen;

[0027] The photocatalyst is one or two of 4DPAIPN and 4CzIPN;

[0028]

[0029] According to the present invention, the R and R" are preferably independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, propoxy, fluorine, chlorine, bromine, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, propionate or isobutylpropionate. 1 , R 1 '、R 1 " is preferably independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or n-hexyl. The R 2 , R 2 '、R 2 " is preferably independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or n-hexyl; said R 3 , R 3 '、R 3 " is preferably independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or n-hexyl. The R 4Preferably, the ester-containing polycyclic quinazolinone derivative has the following structure:

[0030]

[0031]

[0032] It should be noted that the R group and the R" group in the general formula of the N-alkyl olefin quinazolinone compound of the present invention can be substituents at any one or two positions on the benzene ring.

[0033] According to the present invention, an N-alkyl olefin quinazolinone compound, a compound of formula (II), a photocatalyst and a solvent are mixed and reacted under blue light irradiation to obtain a polycyclic quinazolinone derivative containing an ester group; wherein the molar ratio of the N-alkyl olefin quinazolinone compound to the compound of formula (II) is preferably 1:(1.5-4), more preferably 1:(2-3); the molar ratio of the N-alkyl olefin quinazolinone compound to the photocatalyst is preferably 1:(0.001-0.02), more preferably 1:(0.005-0.015); the solvent is preferably N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran and CH 3CN, more preferably one or two of N, N-dimethylformamide and N, N-dimethylacetamide; the N-alkyl olefin quinazolinone compound and the solvent are preferably 1mmol: (8-12)mL, more preferably 1mmol: (9-10)mL; the present invention has no special requirements for the blue light used for reflection, and any blue light source known in the art can be used, preferably a 420-460nm blue LED lamp, more preferably a 20w, 430nm blue LED lamp. The present invention has no special requirements for the mixing method, and any method known to those skilled in the art can be used. The reaction is preferably carried out under a nitrogen atmosphere; wherein the method for providing the nitrogen atmosphere is to remove the air in the reaction solution and the reaction bottle by filling with nitrogen, so that the nitrogen fills the entire reaction system; the reaction time is preferably 5 to 36 hours, more preferably 10 to 24 hours; the reaction temperature is preferably 20 to 30° C., more preferably 25 to 28° C.; after the reaction is completed, the present invention preferably adds saturated saline to quench the reaction, extracts the reaction solution with an organic solvent, and extracts the aqueous phase 2 to 3 times, combines the organic phases, dries, and distills and concentrates to obtain a polycyclic quinazolinone derivative containing an ester group, wherein the organic solvent for extraction is preferably ethyl acetate; the drying agent for drying is preferably anhydrous magnesium sulfate; the present invention also preferably purifies the obtained concentrate again by column chromatography to obtain a high-purity polycyclic quinazolinone derivative containing an ester group, wherein the eluent for column chromatography is preferably petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably (3 to 5):1, and more preferably 4:1.

[0034] The present invention provides a green synthesis method for a polycyclic quinazolinone derivative containing an ester group. The method comprises the following steps: mixing an N-alkyl olefin quinazolinone compound, a compound of formula (II), a photocatalyst and a solvent, and reacting the mixture under blue light irradiation to obtain a polycyclic quinazolinone derivative containing an ester group. Experiments have shown that the method provided by the present invention has a wide range of application to substrates, and that the reaction can occur without the need for activation of highly active functional groups near the reaction sites of the substrates. The reaction conditions are mild and green, and the reaction conversion can be completed under blue light irradiation. The amount of the photocatalyst used is only about 0.5 mol%, and the catalytic efficiency is high. At the same time, the use of a specific photocatalyst not only improves the yield, but also makes the reactants clean and pollution-free. The method has good application prospects and research value.

[0035] The following will be described clearly and completely in conjunction with the technical solutions of the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] All chemicals and solvents were commercially available and used without further purification. Analytical thin layer chromatography (TLC) was performed on silica gel plates (GF254) using UV light (254 nm). For flash chromatography, 200-300 mesh silica gel (Qingdao, China) was used. Recording was at 400 MHz 1 H NMR spectrum. Relative to DMSO-d 6 (δ=2.50ppm), CDCl 3 (δ=7.26ppm), Acteone-d 6 (δ = 2.05 ppm), chemical shifts are in ppm. Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), integration and coupling constant J (Hz). 13 C NMR spectra were recorded at 100 MHz with complete proton decoupling. 6 (δ=39.6ppm), CDCl 3 (δ=77.2ppm), Acteone-d 6 (δ=29.8 ppm), chemical shifts are reported in ppm. 19 F NMR was recorded at 376 MHz. High resolution mass spectra (HRMS) were recorded on a Bruker Apex IV FTMS spectrometer.

[0037] The reaction substrates involved in this embodiment are shown in Table 1:

[0038] Table 1: Substrates involved in the embodiments of the present invention

[0039]

[0040] The substrates involved in the present invention are prepared according to the methods disclosed in the prior art:

[0041] (a) The references used for the synthesis of substrates 1a-1n, 1p-1x, 1z, 1ab and 1ac are as follows: L. Dong, XQ Wang, YH Gou, ZS Yu, Org. Lett., 2024, 26, 8756; the synthesis reaction equation is:

[0042]

[0043] (b) The synthesis method of substrate 1y is as follows: ZS Liu, G. Qian, Q. Gao, P. Wang, HG Cheng, Q. Wei, Q. Zhou, ACS Catal., 2018, 8, 4783, and the reaction equation is:

[0044]

[0045] (c) The method for synthesizing 1o and 1aa is as follows: LK Ackerman, JI Martinez Alvarado, AG Doyle, J. Am. Chem. Soc., 2018, 140, 14059. The reaction equation is as follows:

[0046]

[0047] Example 1

[0048] Br-CH 2 CO 2 t Bu 2a;

[0049] Under nitrogen, compound 1a (0.2 mmol, 1.0 eq), compound 2a (0.4 mmol, 2.0 eq) and 4CzIPN (0.5 mol%) were added to a Schlenk tube and dissolved in 2.0 mL of DMA. The reaction solution was irradiated with a blue LED (430 nm, 20 W) lamp at room temperature for 12 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 30 mL of saturated NaCl. The mixture was extracted with ethyl acetate (EA) three times (3 × 20 mL), and the organic phase was washed with anhydrous MgSO 4 The product was dried and concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: PE / EA = 4 / 1) to obtain 58 mg of ester-containing polycyclic quinazolinone derivative 3a as a yellow solid with a yield of 93%. Figure 1 As shown, Figure 1 The hydrogen spectrum of the compound prepared in Example 1 of the present invention; the carbon spectrum is as follows Figure 2 As shown, Figure 2 This is the carbon spectrum of the compound prepared in Example 1 of the present invention.

[0050] Its chemical structure is:

[0051]

[0052] Characterization data:

[0053] 1 H NMR (400 MHz, CDCl 3): δ8.27-8.25(m,1H),7.73-7.65(m,2H),7.44-7.40(m,1H),4.29-4.22(m,1H),4.03-3.96(m, 1H),3.27-3.23(m,1H),2.52-2.44(m,2H),2.39-2.34(m,2H),1.95-1.89(m,2H),1.44(s,9H);

[0054] 13 C NMR (100 MHz, CDCl 3 ): δ172.2,160.9,160.9,149.2,134.0,127.1,126.3,126.2,120.7,80.5,44.6,43.1,33.0,28.1,27.4,26.4;

[0055] HRMS(ESI)m / z calcd for C 18 H 23 N 2 O 3 [M+H + ]:315.1703,found 315.1699.

[0056] Example 2

[0057] The preparation method and substrate of Example 1 were consistent with those of Example 1. When the amount of each raw material used was the same, the type of reaction catalyst, the reaction solvent or the addition of a base were changed to obtain polycyclic quinazolinone derivatives containing an ester group (see Series 1 to Series 11 in Table 2); Series 12 was obtained under the reaction conditions of Example 1, except that the irradiated blue light was changed to a 470 nm blue LED light to obtain the product; Series 13 was obtained under the reaction conditions of Example 1 except that the blue light was not irradiated to carry out the reaction; Series 14 was obtained under the reaction conditions of Example 1 except that the reaction atmosphere was changed to air; Series 15 was obtained under the reaction conditions of Example 1 except that the substrate 2a (Br-CH 2 CO 2 t Bu) to Cl-CH 2 CO 2 t Bu; the reaction results are shown in Table 2, which is the screening results of the conditions of the present invention.

[0058] Table 2

[0059]

[0060] Example 3

[0061] According to the preparation method of Example 1, different substrates 1 and 2 were selected to prepare a series of polycyclic quinazolinone derivatives containing ester groups, and the results and characterization data are as follows:

[0062]

[0063] Characterization data: light yellow oily liquid, 60 mg, yield 91%.

[0064] 1 H NMR (400 MHz, CDCl 3 ): δ7.55-7.49(m,2H),7.16(d,J=6.8Hz,1H),4.23-4.17(m,1H),3.99-3.92(m,1H),3.26-3.18(m,1H), 2.87(s,3H),2.51-2.46(m,2H),2.44-2.41(m,1H),2.35-2.33(m,1H),1.94-1.86(m,2H),1.45(s,9H);

[0065] 13 C NMR (100 MHz, CDCl 3 ): δ172.2,161.7,160.5,150.9,140.9,133.1,128.8,125.3,119.2,80.5,44.6,43.1,33.1,28.1,27.4,26.3,22.9;

[0066] HRMS(ESI)m / z calcd for C 19 H 25 N 2 O 3 [M+H + ]:329.1860, found 329.1856.

[0067]

[0068] Characterization data: light yellow oily liquid, 58 mg, yield 89%.

[0069] 1 H NMR (400 MHz, CDCl 3): δ8.14(d,J=8.0Hz,1H),7.46(s,1H),7.24(d,J=8.0Hz,1H),4.27-4.20(m,1H),3.99-3.94(m,1H),3.25-3.21 (m,1H),2.51-2.48(m,2H),2.47(s,3H),2.45-2.42(m,1H),2.39-2.33(m,1H),1.93-1.87(m,2H),1.44(s,9H);

[0070] 13 C NMR (100 MHz, CDCl 3 ): δ172.2,160.9,160.9,149.4,144.9,127.8,126.9,126.1,118.3,80.5,44.5,43.1,33.0,28.1,27.4,26.4,21.8;

[0071] HRMS(ESI)m / z calcd for C 19 H 25 N 2 O 3 [M+H + ]:329.1860,found 329.1853.

[0072]

[0073] Characterization data: light yellow oily liquid, 59 mg, yield 90%.

[0074] 1 H NMR (400 MHz, CDCl 3 ): δ8.12(d,J=8.0Hz,1H),7.56(d,J=7.2Hz,1H),7.33-7.29(m,1H),4.29-4.23(m,1H),4.02-3.95(m,1H),3.30-3 .22(m,1H),2.60(s,3H),2.58-2.56(m,2H),2.50-2.42(m,1H),2.38-2.29(m,1H),1.99-1.87(m,2H),1.47(s,9H);

[0075] 13 C NMR (100 MHz, CDCl 3): δ172.4,161.3,159.5,147.8,135.6,134.5,125.6,123.9,120.6,80.4,44.5,42.9,32.9,28.1,27.5,26.7,17.4;

[0076] HRMS(ESI)m / z calcd for C 19 H 25 N 2 O 3 [M+H + ]:329.1860, found 329.1857.

[0077]

[0078] Characterization data: yellow solid, 58 mg, yield 87%.

[0079] 1 H NMR (400 MHz, CDCl 3 ): δ7.90(s,1H),7.38(s,1H),4.27-4.21(m,1H),4.00-3.93(m,1H),3.25-3.20(m,1H),2.56(s,3H),2 .54-2.52(m,1H),2.48-2.43(m,1H),2.41(s,3H),2.34-2.29(m,1H),1.97-1.83(m,2H),1.45(s,9H);

[0080] 13 C NMR (100 MHz, CDCl 3 ): δ172.5,161.3,158.6,145.8,136.1,135.6,135.3,123.3,120.4,80.4,44.4,42.8,33.0,28.1,27.5,26.7,21.1,17.3;

[0081] HRMS(ESI)m / z calcd for C 20 H 27 N 2 O 3 [M+H + ]:343.2016,found 343.2013.

[0082]

[0083] Characterization data: light yellow oily liquid, 65 mg, yield 95%.

[0084] 1 H NMR (400 MHz, CDCl 3 ): δ7.57-7.53(m,2H),7.23-7.20(m,1H),4.23-4.16(m,1H),3.97-3.84(m,1H),3.82(s,3H ),3.21-3.13(m,1H),2.45-2.37(m,3H),2.33-2.25(m,1H),1.89-1.80(m,2H),1.38(s,9H);

[0085] 13 C NMR (100 MHz, CDCl 3 ): δ172.3,160.8,158.7,158.0,143.8,128.6,124.2,121.5,105.8,80.5,55.8,44.6,42.9,33.1,28.1,27.4,26.6;

[0086] HRMS(ESI)m / z calcd for C 19 H 25 N 2 O 4 [M+H + ]:345.1809,found 345.1803.

[0087]

[0088] Characterization data: light yellow oily liquid, 56 mg, yield 84%.

[0089] 1 H NMR (400 MHz, CDCl 3 ): δ7.89(dd,J=8.4,2.8Hz,1H),7.67(dd,J=8.4,4.0Hz,1H),7.43(dd,J=8.0,2.8Hz,1H),4.29-4.22(m,1H), 4.03-3.95(m,1H),3.27-3.22(m,1H),2.52-2.46(m,3H),2.40-2.33(m,1H),1.96-1.87(m,2H),1.45(s,9H);

[0090] 13 C NMR (100 MHz, CDCl 3): δ172.2,160.5(q,J=246Hz),160.3(d,J=1.5Hz),160.2(d,J=3.0Hz),145.9,129.4(d,J=8.2Hz),12 2.5(d,J=23.8Hz),122.0(d,J=8.6Hz),111.2(d,J=23.3Hz),80.6,44.7,43.0,33.0,28.1,27.3,26.5;

[0091] 19 F NMR (376 MHz, CDCl 3 ):δ-113.7;

[0092] HRMS(ESI)m / z calcd for C 18 H 22 FN 2 O 3 [M+H + ]:333.1609,found 333.1606.

[0093]

[0094] Characterization data: light yellow oily liquid, 60 mg, yield 87%.

[0095] 1 H NMR (400 MHz, CDCl 3 ): δ8.38(d,J=2.4Hz,1H),7.77(dd,J=8.8,2.4Hz,1H),7.53(d,J=8.8Hz,1H),4.28-4.02(m,1H),4.00- 3.95(m,1H),3.28-3.20(m,1H),2.51-2.43(m,3H),2.40-2.31(m,1H),1.96-1.86(m,2H),1.45(s,9H);

[0096] 13 C NMR (100 MHz, CDCl 3 ): δ172.1,161.9,159.7,148.1,137.1,129.0,128.8,122.2,119.7,80.6,44.8,43.1,33.0,28.1,27.2,26.4;

[0097] HRMS(ESI)m / z calcd for C 18 H 22 C1N 2 O 3 [M+H+ ]:349.1314, found 349.1310.

[0098]

[0099] Characterization data: light yellow oily liquid, 67 mg, yield 86%.

[0100] 1 H NMR (400 MHz, CDCl 3 ): δ8.23(d,J=2.4Hz,1H),7.66-7.60(m,2H),4.29-4.23(m,1H),4.03-3.96(m,1H),3. 30-3.21(m,1H),2.52-2.45(m,3H),2.39-2.34(m,1H),1.95-1.89(m,2H),1.45(s,9H);

[0101] 13 C NMR (100 MHz, CDCl 3 ): δ172.2,161.3,159.9,147.8,134.4,132.0,128.8,125.7,121.9,80.7,44.8,43.1,33.0,28.1,27.3,26.5;

[0102] HRMS(ESI)m / z calcd for C 18 H 22 Bn 2 O 3 [M+H + ]:393.0808,found 393.0800.

[0103]

[0104] Characterization data: light yellow solid, 65 mg, yield 86%.

[0105] 1 H NMR (400 MHz, DMSO-d 6 ): δ8.28(d,J=8.4Hz,1H),7.93(s,1H),7.74(dd,J=8.4,1.2Hz,1H),4.17-4.11(m,1H),3.95-3.88(m,1H),3. 30-2.3.26(m,1H),2.47-2.43(m,2H),2.40-2.34(m,1H),2.27-2.18(m,1H),1.92-1.73(m,2H),1.40(s,9H);

[0106] 13 C NMR (100 MHz, DMSO-d 6 ): δ171.9,163.7,159.1,149.0,133.7(q,J=32.0Hz),127.4,124.0(d,J=4.1Hz),123. 6(q,J=271.5Hz),123.2,121.6(d,J=3.1Hz),79.7,44.8,42.5,32.2,27.7,26.6,25.6;

[0107] 19 F NMR (376 MHz, DMSO-d 6 ):δ-61.6;

[0108] HRMS(ESI)m / z calcd for C 19 H 22 F 3 N 2 O 3 [M+H + ]:383.1577,found 383.1572.

[0109]

[0110] Characterization data: light yellow solid, 61 mg, yield 93%.

[0111] 1 H NMR (400 MHz, CDCl 3 ): δ8.27(d,J=8.4Hz,1H),7.70-7.67(m,2H),7.44-7.40(m,1H),4.13-4.09(m,2H),2.40-2.36(m,1H), 2.34-2.26(m,1H),2.20-2.13(m,1H),2.11-2.06(m,1H),2.04-1.97(m,2H),1.40(s,3H),1.39(s,9H);

[0112] 13 C NMR (100 MHz, CDCl 3 ): δ172.4,163.4,161.0,149.4,133.9,127.3,126.2,126.1,120.8,80.5,46.0,43.1,33.4,33.1,30.7,28.0,23.9;

[0113] HRMS(ESI)m / z calcd for C19 H 25 N 2 O 3 [M+H + ]:329.1860, found 329.1857.

[0114]

[0115] Characterization data: light yellow solid, 38 mg, yield 56%.

[0116] 1 H NMR (400 MHz, CDCl 3 ): δ8.24(dd,J=8.0,1.2Hz,1H),7.71-7.66(m,1H),7.62-7.60(m,1H),7.41-7.37(m,1H),4.32-4.26(m,1H),3.87-3.80(m ,1H),2.57-2.53(m,1H),2.30-2.17(m,2H),2.15-2.09(m,1H),1.86-1.80(m,1H),1.53(s,3H),1.47(s,9H),1.33(s,3H);

[0117] 13 C NMR (100 MHz, CDCl 3 ): δ171.9,162.7,160.6,147.5,133.9,126.9,126.3,126.0,119.7,80.9,42.3,41.2,38.4,36.6,28.2,28.1,24.2,23.3;

[0118] HRMS(ESI)m / z calcd for C 20 H 27 N 2 O 3 [M+H + ]:343.2016,found 343.2011.

[0119]

[0120] Characterization data: light yellow solid, 66 mg, yield 88%.

[0121] 1 H NMR (400 MHz, CDCl 3): δ8.61(d,J=8.0Hz,1H),8.42(d,J=8.0Hz,1H),7.80–7.77(m,2H),7.54–7.50(m,1H),7.47–7.43(m,1H),7.42–7 .34(m,2H),2.52–2.45(m,1H),2.35–2.27(m,1H),1.91–1.85(m,1H),1.80–1.76(m,1H),1.65(s,3H),1.31(s,9H);

[0122] 13 C NMR (100 MHz, CDCl 3 ): δ171.8,162.9,160.0,147.5,139.1,135.2,134.3,128.7,127.5,126. 8,126.7,122.7,121.4,117.2,80.5,48.4,35.0,30.5,27.9,26.9,26.0;

[0123] HRMS(ESI)m / z calcd for C 23 H 25 N 2 O 3 [M+H + ]:377.1860, found 377.1861.

[0124]

[0125] Characterization data: light yellow oily liquid, 42 mg, yield 65%.

[0126] 1 H NMR (400 MHz, CDCl 3 ): δ7.74(d,J=5.2Hz,1H),7.28(d,J=5.2Hz,1H),4.31-4.25(m,1H),4.04-3.97(m,1H),3 .31–3.23(m,1H),2.50-2.47(m,3H),2.38-2.32(m,1H),2.00-1.88(m,2H),1.44(s,9H);

[0127] 13 C NMR (100 MHz, CDCl 3 ): δ172.1,162.9,158.3,157.1,133.8,124.8,121.5,80.6,44.6,42.8,32.9,28.1,27.4,26.9;

[0128] HRMS(ESI)m / z calcd for C 16 H 21 N 2 O 3 S[M+H + ]:321.1267, found 321.1272.

[0129]

[0130] Characterization data: light yellow oily liquid, 88 mg, yield 92%.

[0131] 1 H NMR (400 MHz, CDCl 3 ): δ7.87(d,J=2.4Hz,1H),7.62(d,J=8.0Hz,1H),7.33(dd,J=8.8,2.4Hz,1H),7.29(d,J= 8.4Hz,2H),7.14(d,J=8.0Hz,2H),4.26-4.20(m,1H),4.00-3.92(m,2H),3.66(s,3H),3.2 8-3.20(m,1H),2.62-2.58(m,2H),2.47-2.45(m,2H),2.43-2.39(m,1H),2.37-2.32(m,1H ),1.99-1.91(m,1H),1.90-1.83(m,2H),1.61(d,J=7.2Hz,3H),0.91(s,3H),0.89(s,3H);

[0132] 13 C NMR (100 MHz, CDCl 3 ): δ173.2,173.0,160.5,160.2,148.7,146.9,140.9,136.9,129.5,128.3,128.2,12 7.1,121.4,118.1,51.6,45.1,45.0,44.6,42.8,31.4,30.1,27.2,26.4,22.3,18.4;

[0133] HRMS(ESI)m / z calcd for C 28 H 33 N 2 O 5 [M+H + ]:477.2384,found 477.2376.

[0134]

[0135] Characterization data: light yellow solid, 52 mg, yield 80%.

[0136] 1 H NMR (400 MHz, CDCl 3 ): δ8.23(dd,J=8.0,1.2Hz,1H),7.70-7.66(m,1H),7.62-7.60(m,1H),7.41-7.37(m,1H),4.27-4.21(m,1H),3.95-3.88(m,1H), 2.93–2.89(m,1H),2.49-2.41(m,2H),2.39-2.37(m,1H),2.13-2.01(m,1H),1.99-1.91(m,3H),1.66-1.61(m,1H),1.42(s,9H);

[0137] 13 C NMR (100 MHz, CDCl 3 ): δ172.7,162.1,156.9,147.3,133.9,126.9,126.5,126.1,120.2,80.3,41.5,39.7,33.2,28.3,28.0,24.9,20.1;

[0138] HRMS(ESI)m / z calcd for C 19 H 25 N 2 O 3 [M+H + ]:329.1860, found 329.1857.

[0139]

[0140] Characterization data: light yellow oily liquid, 51 mg, yield 74%.

[0141] 1 H NMR (400 MHz, CDCl 3 ): δ7.52(t,J=7.6Hz,1H),7.45(d,J=7.6Hz,1H),7.16(d,J=7.2Hz,1H),4.17-4.11(m,1H),3.91-3.85(m,1H),2.90-2.87(m,1 H),2.85(s,3H),2.48-2.44(m,2H),2.43-2.36(m,1H),2.11-2.05(m,1H),2.03-1.90(m,3H),1.66-1.59(m,1H),1.43(s,9H);

[0142] 13 C NMR (100 MHz, CDCl 3 ): δ172.8,162.7,156.5,148.8,140.7,133.0,128.6,125.1,118.8,80.3,41.4,39.6,33.2,28.4,28.1,24.9,23.1,20.3;

[0143] HRMS(ESI)m / z calcd for C 20 H 27 N 2 O 3 [M+H + ]:343.2016, found 343.2019.

[0144]

[0145] Characterization data: light yellow solid, 60 mg, yield 87%.

[0146] 1 H NMR (400 MHz, CDCl 3 ): δ8.12(d,J=8.0Hz,1H),7.43(s,1H),7.23(d,J=8.0Hz,1H),4.28-4.21(m,1H),3.94-3.87(m,1H),2.92-2.88(m,1H),2.50-2.49 (m,1H),2.47(s,3H),2.46-2.37(m,1H),2.13-2.07(m,1H),2.08-1.98(m,1H),1.97-1.91(m,3H),1.66-1.59(m,1H),1.43(s,9H);

[0147] 13 C NMR (100 MHz, CDCl 3 ): δ172.8,162.1,157.0,147.4,144.8,127.7,126.6,126.4,117.9,80.3,41.4,39.7,33.2,28.4,28.1,25.0,21.8,20.2;

[0148] HRMS(ESI)m / z calcd for C 20 H 27 N 2 O 3 [M+H +]:343.2016,found 343.2013.

[0149]

[0150] Characterization data: light yellow solid, 58 mg, yield 92%.

[0151] 1 H NMR (400 MHz, CDCl 3 ): δ7.59(d,J=2.8Hz,1H),7.54(d,J=8.8Hz,1H),7.29(dd,J=8.8,2.8Hz,1H),4.31-4.24(m,1H),3.94-3.90(m,1H),3.89(s,3H) ,3.63(s,3H),2.93-2.86(m,1H),2.61-2.56(m,2H),2.47-2.38(m,1H),2.15-2.07(m,1H),2.03-1.96(m,3H),1.67-1.58(m,1H);

[0152] 13 C NMR (100 MHz, CDCl 3 ): δ173.8,161.9,157.9,154.4,141.9,128.5,124.4,120.8,105.6,55.7,51.5,41.5,39.4,31.8,28.2,25.1,20.2;

[0153] HRMS(ESI)m / z calcd for C 17 H 21 N 2 O 4 [M+H + ]:317.1496,found 317.1491.

[0154]

[0155] Characterization data: light yellow oily liquid, 66 mg, yield 95%.

[0156] 1 H NMR (400 MHz, CDCl 3): δ7.55(s,1H),7.01(s,1H),4.29-4.22(m,1H),3.98(s,3H),3.97(s,3H),3.95-3.88(m,1H),3.65(s,3H),2.9 3-2.86(m,1H),2.61-2.57(m,2H),2.48-2.39(m,1H),2.15-2.07(m,1H),2.03-1.94(m,3H),1.66-1.58(m,1H);

[0157] 13 C NMR (100 MHz, CDCl 3 ): δ173.8,161.4,155.5,154.8,148.7,143.6,125.0,113.5,107.2,105.4,56.2,51.6,41.5,39.5,31.8,28.3,25.1,20.2;

[0158] HRMS(ESI)m / z calcd for C 18 H 23 N 2 O 5 [M+H + ]:347.1602,found 347.1596.

[0159]

[0160] Characterization data: light yellow solid, 67 mg, yield 87%.

[0161] 1 H NMR (400 MHz, CDCl 3 ): δ8.32-8.29(m,2H),8.02(dd,J=8.4,1.6Hz,1H),4.32-4.25(m,1H),3.97(s,3H),3.94-3.91(m,1H),2.95-2.92( m,1H),2.53-2.51(m,2H),2.49-2.39(m,1H),2.17-2.12(m,1H),2.05-1.95(m,3H),1.68-1.63(m,1H),1.45(s,9H);

[0162] 13 C NMR (100 MHz, CDCl 3): δ172.7,166.3,161.7,157.9,147.1,135.1,129.0,126.9,126.1,123.2,80.4,52.5,41.7,39.7,33.2,28.3,28.1,25.0,20.2;

[0163] HRMS(ESI)m / z calcd for C 21 H 27 N 2 O 5 [M+H + ]:387.1914, found 387.1913.

[0164]

[0165] Characterization data: light yellow solid, 57 mg, yield 82%.

[0166] 1 H NMR (400 MHz, CDCl 3 ): δ7.82(dd,J=8.4,2.8Hz,1H),7.59(dd,J=8.8,4.0Hz,1H),7.40(dd,J=8.4,3.2Hz,1H),4.25–4.19(m,1H),3.92–3.85(m,1H), 2.90–2.86(m,1H),2.47–2.40(m,2H),2.38–2.35(m,1H),2.12-2.07(m,1H),1.99–1.90(m,3H),1.64-1.60(m,1H),1.40(s,9H);

[0167] 13 C NMR (100 MHz, CDCl 3 ): δ172.6,161.4(d,J=3.4Hz),160.3(q,J=246Hz),156.6,156.2(d,J=1.5Hz),143.9,129.3(d,J=8.2Hz),12 2.5(d,J=24.1Hz),121.2(d,J=8.5Hz),111.1(d,J=23.4Hz),80.3,41.6,39.5,33.1,28.2,28.0,24.8,20.1;

[0168] 19 F NMR (376 MHz, CDCl 3 ):-113.7;

[0169] HRMS(ESI)m / z calcd for C 19 H 24 FN 2 O 3 [M+H + ]:347.1765,found 347.1762.

[0170]

[0171] Characterization data: light yellow solid, 67 mg, yield 93%.

[0172] 1 H NMR (400 MHz, CDCl 3 ): δ8.10(d,J=2.4Hz,1H),7.55(dd,J=8.8,2.4Hz,1H),7.49(d,J=8.8Hz,1H),4.22-4.15(m,1H),3.88-3.82(m,1H),2.89- 2.82(m,1H),2.45-2.41(m,2H),2.38-2.33(m,1H),2.10-2.05(m,1H),1.97-1.87(m,3H),1.63-1.54(m,1H),1.38(s,9H);

[0173] 13 C NMR (100 MHz, CDCl 3 ): δ172.5.160.9,157.2,145.6,134.2,131.5,128.5,125.6,121.0,80.2,41.5,39.5,33.0,28.1,27.9,24.7,20.0;

[0174] HRMS(ESI)m / z calcd for C 19 H 24 C1N 2 O 3 [M+H + ]:363.1470,found 363.1468.

[0175]

[0176] Characterization data: light yellow solid, 56 mg, yield 71%.

[0177] 1 H NMR (400 MHz, CDCl 3): δ8.35(d,J=8.0Hz,1H),7.92(s,1H),7.61(d,J=9.6Hz,1H),4.32–4.25(m,1H),3.96–3.90(m,1H),2.98–2.93(m ,1H),2.50-2.48(m,2H),2.44–2.37(m,1H),2.18-2.13(m,1H),2.05–1.94(m,3H),1.70–1.61(m,1H),1.44(s,9H);

[0178] 13 C NMR (100 MHz, CDCl 3 ): δ172.7,161.4,158.6,147.2,135.5(q,J=32.5Hz),127.8,124.6(q,J=3.8Hz),123.5(q ,J=271.4Hz),122.5,122.0(q,J=3.5Hz),80.4,41.7,39.8,33.1,28.2,28.1,24.9,20.1;

[0179] 19 F NMR (376 MHz, CDCl 3 ):δ-63.1;

[0180] HRMS(ESI)m / z calcd for C 20 H 24 F 3 N 2 O 3 [M+H + ]:397.1734,found 397.1730.

[0181]

[0182] Characterization data: light yellow liquid, 60 mg, yield 95%.

[0183] 1 H NMR (400 MHz, CDCl 3): δ8.22(dd,J=8.0,1.2Hz,1H),7.69(td,J=8.0,1.6Hz,1H),7.60(d,J=8.0Hz,1H),7.40(td,J=8.0,1.2Hz,1H),4.08-4.0 0(m,2H),3.52(s,3H),2.47-2.41(m,1H),2.34-2.22(m,2H),2.12-1.89(m,5H),1.80-1.73(m,2H),0.86(t,J=7.6Hz,3H);

[0184] 13 C NMR (100 MHz, CDCl 3 ): δ174.0,162.7,158.6,147.1,133.8,127.1,126.3,126.1,119.7,51.5,43.6,43.5,34.7,33.1,29.3,28.7,18.9,8.4;

[0185] HRMS(ESI)m / z calcd for C 18 H 23 N 2 O 3 [M+H + ]:315.1703,found 315.1712.

[0186]

[0187] Characterization data: light yellow oily liquid, 37 mg, yield 56%.

[0188] 1 H NMR (400 MHz, CDCl 3 ): δ7.72(d,J=5.2Hz,1H),7.25(d,J=5.2Hz,1H),4.33-4.27(m,1H),3.94–3.87(m,1H),2.96-2.89(m,1H),2 .51–2.40(m,2H),2.38–2.34(m,1H),2.15-2.07(m,1H),2.01–1.93(m,2H),1.66–1.57(m,2H),1.42(s,9H);

[0189] 13 C NMR (100 MHz, CDCl 3): δ172.6,158.7,158.3,156.1,133.9,124.9,120.8,80.4,41.3,41.0,39.6,33.1,28.4,28.0,24.8,20.1;

[0190] HRMS(ESI)m / z calcd for C 17 H 23 N 2 O 3 S[M+H + ]:335.1424,found 335.1425.

[0191]

[0192] Characterization data: light yellow oily liquid, 87 mg, yield 89%.

[0193] 1 H NMR (400 MHz, CDCl 3 ): δ7.85(d,J=2.8Hz,1H),7.59(d,J=8.8Hz,1H),7.33(dd,J=8.8,2.8Hz,1H),7.30(d,J=8.4Hz,2H), 7.15(d,J=8.4Hz,2H),4.28-4.22(m,1H),3.94(q,J=7.2Hz,1H),3.91-3.84(m,1H),3.63(s,3H),2.9 2-2.87(m,1H),2.60-2.56(m,2H),2.47(d,J=7.2Hz,2H),2.44-2.37(m,1H),2.14-2.07(m,1H),2.04 -1.93(m,3H),1.90-1.82(m,1H),1.67-1.60(m,1H),1.61(d,J=7.2Hz,3H),0.92(s,3H),0.90(s,3H);

[0194] 13 C NMR (100 MHz, CDCl 3 ): δ173.8,173.0,161.5,156.5,148.6,145.0,140.9,136.9,129.5,128.3,127.1,1 20.8,118.2,51.5,45.2,45.0,41.5,39.4,31.7,30.1,28.1,25.0,22.4,20.1,18.5;

[0195] HRMS(ESI)m / z calcd for C29 H 35 N 2 O 5 [M+H + ]:491.2540,found 491.2542.

[0196]

[0197] Characterization data: light yellow oily liquid, 35 mg, yield 58%.

[0198] 1 H NMR (400 MHz, CDCl 3 ): δ8.23(dd,J=8.0,1.2Hz,1H),7.67(td,J=8.0,1.2Hz,1H),7.61(d,J=8.0Hz,1H),7.41(td,J=8.0,1.2Hz,1H),5.20-5.10(m,1H ),3.65(s,3H),3.62-3.58(m,1H),3.09-3.07(m,1H),2.63-2.47(m,3H),2.04-1.89(m,4H),1.88-1.85(m,1H),1.77-1.48(m,2H);

[0199] 13 C NMR (100 MHz, CDCl 3 ): δ174.2,162.1,159.3,147.1,133.9,127.2,126.8,126.3,120.3,51.5,43.2,41.3,32.6,32.0,28.6,28.0,27.2;

[0200] HRMS(ESI)m / z calcd for C 17 H 21 N 2 O 3 [M+H + ]:301.1547,found 301.1540.

[0201] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A green synthesis method of a polycyclic quinazolinone derivative containing an ester group, comprising: An N-alkyl olefin quinazolinone compound, a compound of formula (II), a photocatalyst and a solvent are mixed and reacted under blue light irradiation to obtain a polycyclic quinazolinone derivative containing an ester group; The N-alkyl olefin quinazolinone compound is of formula (Ia), formula (Ib) or formula (Ic) Br-CH2CO2R4 formula (II); The ester-containing polycyclic quinazolinone derivative is of formula (III-a), formula (III-b) or formula (III-c), in, Said n, n' are independently selected from 1, 2 or 3; The R and R" are independently selected from hydrogen, C1-C6 alkyl with substituents, C1-C6 alkyl without substituents, C1-C3 alkoxy, halogen, C2-C15 carboxylate or C2-C5 alkoxycarbonyl; The R1, R1', and R1" are independently selected from hydrogen or a C1-C3 alkyl group without a substituent; The R2, R2', and R2" are independently selected from hydrogen or a C1-C3 alkyl group without a substituent; The R3, R3', and R3" are independently selected from hydrogen or a C1-C3 alkyl group without a substituent; The R4 is a C1-C6 alkyl group without a substituent; The X is sulfur or oxygen; The photocatalyst is one or both of 4DPAIPN and 4CzIPN.

2. The preparation method according to claim 1, characterized in that: The R and R" are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, propoxy, fluorine, chlorine, bromine, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, propionate or isobutylpropionate.

3. The preparation method according to claim 1, characterized in that: The R1, R1', R1" are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or n-hexyl.

4. The preparation method according to claim 1, characterized in that: Said R2, R2', R2" are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or n-hexyl; The R3, R3' and R3" are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or n-hexyl.

5. The preparation method according to claim 1, characterized in that: The R4 is methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or n-hexyl.

6. The preparation method according to claim 1, characterized in that: The molar ratio of the N-alkyl olefin quinazolinone compound to the compound of the formula (II) is 1:(1.5-4).

7. The preparation method according to claim 1, characterized in that: The molar ratio of the N-alkyl olefin quinazolinone compound to the photocatalyst is 1:(0.001-0.010).

8. The preparation method according to claim 1, characterized in that: The solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran and CH3CN.

9. The preparation method according to claim 2, characterized in that: The ratio of the N-alkyl olefin quinazolinone compound to the solvent is 1 mmol: (8-12) mL.

10. The preparation method according to claim 1, characterized in that: The polycyclic quinazolinone derivative containing an ester group has the following structure:

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