N-(2-organoselenyl)acrylquinazolinone and preparation method thereof

Abstract

The invention provides a kind of N-(2-organoselenyl) acrylaldehyde quinazolinone and its preparation method. The preparation method comprises the following steps: using tert-butyl hydroperoxide (TBHP) as an oxidant, aryl propargyl quinazolinone ether and diaryl (alkyl) diselenide react to efficiently obtain N-(2-organoselenyl) acrylaldehyde quinazolinone. The preparation method has mild reaction conditions, simple operation, low cost, good product yield and high purity, is easy to separate and purify, and can be suitable for large-scale preparation; the product structure contains organic selenium and quinazolinone pharmacophoric group skeleton, has a broad spectrum of biological activity, and this type of compound has very good application prospects in the research and development of anticancer drugs.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemistry, and in particular to an organic selenium-substituted quinazolinone and a preparation method thereof. Background Art

[0002] Quinazolinone is an important class of heterocyclic compounds, and its skeleton is widely present in many natural products. These natural compounds and their derivatives have multiple biological activities such as anticancer, antibacterial, anti-inflammatory, and antimalarial. Currently available anticancer drugs such as erlotinib, gefitinib, lapatinib, Zydelig / Idelalisib, etc. all contain quinazoline skeleton [(a) Gatadi, S.; Lakshmi, TV; Nanduri, S. Eur. J. Med. Chem. 2019, 170, 157-172. (b) A. Hameed, M. Al-Rashida, M. Uroos, S. A. Ali, Arshia, M. Ishtiaq and K. M. Han, Expert Opin. Ther. Pat., 2018, 28, 281-297. (c) Ghorab, MM, Alqahtani, AS, Soliman, AM., Askar, AAInt. J. Nanomed. 2020, 15, 3161-3180. (d) Soliman, AM, Karam, HM., Mekkawy, MH, Ghorab, MM Eur. J. Med. Chem. 2020, 197, 112333. (e) Plescia, F.; Maggio, B.; Daidone, G.; Raffa, D. Eur. J. Med. Chem., 2021, 213, 113070.]. Therefore, the research on the synthesis method of quinazolinone derivatives has received more and more attention.

[0003]

[0004]

[0005] On the other hand, organic selenium compounds play an important role as synthetic intermediates in the development of biologically active organic drugs. Introducing selenium atoms into organic molecules can change the physical and chemical reactivity, pharmacology and toxicity of the molecules. Therefore, splicing organic selenium into organic compound molecules has always been a rich research hotspot in the field of synthesizing selenium-containing drugs. For example, the following are some biologically active organic selenium heterocyclic compound molecules:

[0006]

[0007] At present, there are relevant literature reports on the successful connection of organic selenium to organic molecules [(a) Shi, Q., Li, P., Zhang, Y., Wang, L., Org. Chem. Front. 2017, 4, 1322-1331; b) Sahoo, H., Mandal, A.,, Dana, Baiduya, S., M., Adv. Synth. Catal. 2018, 360, 1099-1103; c) Sahoo o, H., Singh, S., Baidya, M., Org. Lett. 2018, 20, 3678-3681; d) Fang, JD, Yan, XB, Zhou, L., Wang, YZ, Liu, XY, Adv. Synth. Catal. 2019, 361, 1985-1990.], wherein diselenide is used to generate selenium radicals, which are added to the carbon-carbon triple bond and then rearranged to synthesize organic selenium-substituted compounds. In view of the biological activity of quinazolinone and organic selenium compounds, and the fact that there is no report on the construction of organic selenium-substituted quinazolinone, it is of great research value and practical significance to develop new organic synthesis methods and construct organic selenium-substituted quinazolinone. Summary of the invention

[0008] Based on this, the present invention aims to provide an N-(2-organoselenyl)acrylaldehyde quinazolinone and a preparation method thereof, which at least solves one problem in the prior art.

[0009] The present invention provides an N-(2-organoselenyl)acryl quinazolinone having a structure shown in the following formula:

[0010]

[0011] in,

[0012] R 1 is an aromatic substituent or heteroaryl group containing an electron donating group or an electron withdrawing group;

[0013] R 2 is H, an electron donating group or an electron withdrawing group;

[0014] R 3 is an aromatic substituent containing an electron donating group or an electron withdrawing group;

[0015] R 4 is an alkyl group or an aromatic substituent containing an electron donating group or an electron withdrawing group;

[0016] The electron-donating group is C1-C8 alkyl, C1-C8 alkoxy, etc.; the electron-withdrawing group is halogen or trifluoromethyl, etc.; the heteroaryl group is pyridyl, thienyl or furyl, etc.

[0017] The preparation method of N-(2-organoselenyl)acryl quinazolinone provided by the present invention comprises the following steps:

[0018] Under the action of an oxidant, the aryl propargyl quinazoline ether shown in Formula 1 and the diaryl (alkyl) diselenide ether shown in Formula 2 react in a solvent to obtain N-(2-organoselenyl) acryl quinazoline ketone shown in Formula 3;

[0019]

[0020] in,

[0021] R 1 is an aromatic substituent or heteroaryl group containing an electron donating group or an electron withdrawing group;

[0022] R 2 is H, an electron donating group or an electron withdrawing group;

[0023] R 3 is an aromatic substituent containing an electron donating group or an electron withdrawing group;

[0024] R 4 is an alkyl group or an aromatic substituent containing an electron donating group or an electron withdrawing group;

[0025] The electron-donating group is C1-C8 alkyl, C1-C8 alkoxy, etc.; the electron-withdrawing group is halogen or trifluoromethyl, etc.; the heteroaryl group is pyridyl, thienyl or furyl, etc.

[0026] The present invention also provides the use of the N-(2-organoselenyl)acrylaldehyde quinazolinone in preparing a drug for inhibiting tumors, for example, for preparing a drug for inhibiting lung tumors. The N-(2-organoselenyl)acrylaldehyde quinazolinone is prepared into a drug for inhibiting tumor growth, increasing apoptosis of tumor cells, having antiproliferative activity against human cancer cells and showing strong activity against tubulin polymerization.

[0027] Due to the adoption of the above technical scheme, the embodiments of the present invention have at least the following beneficial effects: the preparation method of N-(2-organoselenyl)acrylaldehyde quinazolinone is simple to operate, the substrate has good applicability, the conditions are very mild, the yield of the product is good, the purity is high, the reaction efficiency can be as high as 99%, which is conducive to separation and purification, and can be applicable to large-scale production and preparation; the atom economy of the reaction is very high, reflecting a good green process; N-(2-organoselenyl)acrylaldehyde quinazolinone contains organic selenium and quinazolinone pharmacophore skeleton, has a wide range of biological activities, and therefore has very good application prospects in the research and development of anticancer drugs. DETAILED DESCRIPTION

[0028] The following is a clear and complete description of the concept of the present invention and the technical effects produced, so as to fully explain the purpose, scheme and effect of the present invention.

[0029] The inventors have found that N-(2-organoselenyl)acryl quinazolinone compounds can be synthesized by using tert-butyl hydroperoxide as an oxidant, aryl propargyl quinazoline ether and diaryl (alkyl) diselenide as raw materials through a free radical cascade reaction, and the reaction formula is as follows:

[0030]

[0031] in,

[0032] R 1 is an aromatic substituent or heteroaryl group containing an electron donating group or an electron withdrawing group;

[0033] R 2 is H, an electron donating group or an electron withdrawing group;

[0034] R 3 is an aromatic substituent containing an electron donating group or an electron withdrawing group;

[0035] R 4 is an alkyl group or an aromatic substituent containing an electron donating group or an electron withdrawing group;

[0036] The electron-donating group is C1-C8 alkyl, C1-C8 alkoxy, etc.; the electron-withdrawing group is halogen or trifluoromethyl, etc.; the heteroaryl group is pyridyl, thienyl or furyl, etc.

[0037] In some preferred embodiments, the electron donating group is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, etc.; the electron withdrawing group is selected from fluorine, chlorine, bromine, iodine or trifluoromethyl, etc.; the aromatic substituent is selected from phenyl, naphthyl, anthracenyl, phenanthrenyl, biphenyl, etc.; the heteroaryl is selected from pyridyl, thienyl, furanyl, etc.

[0038] In some more preferred embodiments, the R 1 is selected from phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, p-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, m-methylphenyl, m-methoxyphenyl, 3-fluorophenyl, 3-chlorophenyl, o-methylphenyl, thienyl, and pyridyl; said R 2 is selected from hydrogen, methyl, methoxy, fluorine, chlorine, and bromine; said R 3 is selected from phenyl, p-methoxyphenyl, p-methylphenyl, 4-chlorophenyl, 4-bromophenyl; said R 4 Selected from phenyl, p-methylphenyl, p-methoxyphenyl, p-tert-butylphenyl, 2,4,6-trimethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, methyl and ethyl.

[0039] In some preferred embodiments, the oxidant is tert-butyl hydroperoxide (TBHP).

[0040] In some preferred embodiments, the molar ratio of the aryl propargyl quinazoline ether to the diaryl (alkyl) diselenide is 1: 1 to 2, and the molar ratio of the aryl propargyl quinazoline ether to the oxidant is 1: 1 to 3. Most preferably, the molar ratio of the aryl propargyl quinazoline ether to the diaryl (alkyl) diselenide is 1: 1.1, and the molar ratio of the aryl propargyl quinazoline ether to the oxidant is 1: 1.5.

[0041] In some preferred embodiments, the solvent is acetonitrile.

[0042] In some preferred embodiments, the reaction is carried out at 50° C. to 70° C. Most preferably, the reaction is carried out at 60° C.

[0043] In some preferred embodiments, the specific operation steps for synthesizing N-(2-organoselenyl)acrylaldehyde quinazolinone compounds are as follows: aryl propargyl quinazolinone ether, diaryl (alkyl) diselenide and tert-butyl hydroperoxide are placed in a dry and clean reaction tube, acetonitrile solvent is added, and the reaction solution is placed at 60° C. for 12 hours. The reaction raw materials completely disappear according to TLC detection, the solvent is spin-dried under reduced pressure, and the product is separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 6:1) to obtain the desired product.

[0044] Some typical embodiments are listed below.

[0045] Example 1

[0046] Phenyl propargyl quinazoline ether, diphenyl diselenide and tert-butyl hydroperoxide were placed in a dry and clean reaction test tube, and acetonitrile solvent was added. The reaction solution was placed at 60° C. for 12 hours. TLC detection showed that the reaction raw materials completely disappeared. The solvent was dried under reduced pressure, and the product was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 6:1) to obtain the product N-(2-organoselenyl) acryl quinazoline 3aa.

[0047]

[0048] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3aa,E / Z=97 / 3)

[0049] N-(2-Organoselenyl)acryl quinazolinone 3aa is a yellow solid with a yield of 99% and a melting point (mp): 122.9-123.8°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0050] 1 H NMR (400MHz, CDCl3) δ9.61 (s, 0.97H), 9.36 (s, 0.03H), 8.39 (d, J = 7.6Hz, 1H), 7.84-7.77 (m, 2H), 7.56 (ddd, J = 8. 0,6.8,1.2Hz,1H),7.43-7.41(m,2H),7.24-7.17(m,6H),7.11-7.05(m,4H),6.82(d,J=7.2Hz,2H),2.36(s,3H).

[0051] 13 C NMR (100MHz, CDCl3) δ188.8,161.5,154.6,147.2,144.8,140.3,136.4,135.2,133.0,132.3,13 1.7,130.0,129.5,129.2,128.9,128.8,128.3,128.0,127.9,127.7,127.6,127.5,120.1,21.5.

[0052] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 23 N2O2Se + :523.0919, found 523.0906.

[0053] Only the reactants were changed and Examples 3ba-3ya were obtained in the same manner.

[0054] Example 2

[0055]

[0056] 2-Phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ba,E / Z=97 / 3)

[0057] The product 3ba is a yellow solid with a yield of 92% and a melting point (mp): 72.3-73.1°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0058] 1 H NMR (400MHz, CDCl3) δ9.61 (s, 0.97H), 9.35 (s, 0.3H), 8.40 (d, J = 7.6Hz, 1H), 7.84-7.77 (m, 2H), 7.56 (t, J = 7.6Hz, 1H), 7.45- 7.43(m,2H),7.37(t,J=7.2Hz,1H),7.29-7.18(m,8H),7.09-7.05(m,2H),6.83(d,J=7.6Hz,0.2H),6.79(d,J=7.6Hz,1.8H).

[0059] 13 C NMR (100MHz, CDCl3) δ188.9,161.4,154.4,147.1,144.3,136.4,135.8,135.3,133.4,132.3, 131.7,130.0,129.5,129.1,128.9,128.3,128.2,128.0,127.9,127.8,127.7,127.6,120.2.

[0060] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 21 N2O2Se + :509.0763,found 509.0770.

[0061] Example 3

[0062]

[0063] 2-(p-Isopropyl)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ca,E / Z=95 / 5)

[0064] The product 3ca is a yellow solid with a yield of 88% and a melting point (mp): 173.1-174.0°C. Its NMR and mass spectrometry experimental data are as follows:

[0065] 1 H NMR (400MHz, CDCl3) δ9.63 (s, 0.95H), 9.34 (s, 0.05H), 8.40 (d, J = 8.0Hz, 1H), 7.8-7.76 (m, 2H), 7.55 (t, J = 7.6Hz, 1H), 7 .46-7.44(m,2H),7.24-7.18(m,6H),7.10-7.02(m,4H),6.75(d,J=8.0Hz,2H),2.93-2.87(m,1H),1.23(d,J=6.8Hz,6H).

[0066] 13 C NMR (100MHz, CDCl3) δ188.8,161.4,154.5,151.4,147.2,144.8,136.5,135.2,133.3,132.3,131.7,1 29.9,129.5,129.3,128.8,128.4,128.0,127.8,127.7,127.6,127.5,126.3,120.1,34.1,24.0,23.9.

[0067] HRMS(ESI):m / z[M+H] + Calculate for C 32 H 27 N2O2Se + :551.1232, found 551.1235.

[0068] Example 4

[0069]

[0070] 2-(p-tert-Butry)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3da,E / Z=87 / 13)

[0071] The product 3da is a yellow solid with a yield of 97% and a melting point (mp): 208.3-209.0°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0072] 1 H NMR (400MHz, CDCl3) δ9.64 (s, 0.87H), 9.34 (s, 0.13H), 8.40 (d, J = 7.6Hz, 1H), 7.83-7.76 (m, 2H), 7.60 (d, J = 7.6Hz, 0.34H), 7.55 (t, J = 6.8Hz, 1H), 7 .44(d,J=7.6Hz,1.66H)7.25-7.13(m,8H),7.05-7.02(m,2H),6.81(d,J=7 .6Hz,0.34H),6.73(d,J=7,6Hz,1.66H),1.31(s,7.50H),1.29(s,1.50H).

[0073] 13 C NMR (100MHz, CDCl3) δ188.8,188.7,161.4,160.4,154.5,154.4,153.7,153.6,14 7.3,147.2,144.9,138.0,136.6,135.2,135.1,133.6,133.0,132.3,131.7,130. 7,129.9,129.8,129.5,129.3,129.2,128.8,128.5,128.3,128.1,128.0,127.9,127.8,127.7,127.6,127.5,127.4,125.2,125.1,120.6,120.2,34.8,31.3,31.2.

[0074] HRMS(ESI):m / z[M+H] + Calculate for C 33 H 29 N2O2Se + :565.1389,found 565.1383.

[0075] Example 5

[0076]

[0077] 2-(p-Methoxy)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ea,E / Z=75 / 25)

[0078] The product 3ea is a yellow solid with a yield of 93% and a melting point (mp): 76.3-77.2°C. Its NMR and mass spectrometry experimental data are as follows:

[0079] 1 H NMR (400MHz, CDCl3) δ9.63 (s, 0.75H), 9.37 (s, 0.25H), 8.38 (d, J = 7.6Hz, 1H), 7.82-7.75 (m, 2H), 7.58-7.44 (m, 3H), 7.28-7.07 (m, 8H) ,6.91(d,J=7.6Hz,0.5H),6.82(d,J=7.6Hz,1.5H),6.77(d,J=8.4Hz,1.5H),6.72(d,J=8.4Hz,0.5H),3.80(s,2.25H),3.78(s,0.75H).

[0080] 13 C NMR (100MHz, CDCl3) δ188.9,188.8,161.5,161.1,161.0,160.5,154.3,154.1,1 47.3,147.2,144.7,137.8,136.5,135.3,135.2,135.1,133.4,132.3,131.6,13 0.8,130.1,130.0,129.9,129.8,129.5,129.2,128.8,128.7,128.4,128.0,127.9,127.8,127.7,127.6,127.5,127.4,120.3,120.0,113.7,113.6,55.5,55.4.

[0081] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 23 N2O3Se + :539.0868, found 539.0854.

[0082] Example 6

[0083]

[0084] 2-(p-Fluoro)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3fa,E / Z=92 / 8)

[0085] The product 3fa is a yellow solid with a yield of 89% and a melting point (mp): 71.5-72.4°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0086] 1 H NMR (400MHz, CDCl3) δ9.57(s,0.92H),9.37(s,0.08H),8.39(dd,J=8.0,0.8Hz,1H),7.81(ddd,J=8.0,6.8,1.2Hz,1H),7.76(d,J=8.0Hz,1H),7.56(dd d,J=8.0,7.2,1.2Hz,1H),7.48-7.45(m,2H),7.33-7.30(m,2H),7.26-7.20 (m,4H),7.13-7.09(m,2H),6.96-6.92(m,2H),6.81(dd,J=8.4,1.2Hz,2H).

[0087] 13 C NMR (100MHz, CDCl3) δ189.2,188.5,163.6(d, 1 J=249.9Hz),161.2,153.5,147.0,142.9,136.3,135.3,133.4,132.6,132.1(d, 4 J=3.4Hz),131.7,130.6(d, 3 J=8.6Hz),130.4(d, 3 J=8.4Hz),130.1,129.9,129.6,129.2,128.9,128.8,128.7,128.1,128.0,127.9(d, 4 J=3.9Hz),127.8,127.7,120.2,115.4(d, 2 J=21.8Hz),115.3(d, 2 J=21.9Hz).

[0088] 19F NMR(376MHz, CDCl3)δ-108.87,-108.89,-108.90,-108.91,-108.92,-108.93 ,-108.95,-109.25,-109.27,-109.28,-109.29,-109.30,-109.31,-109.33.

[0089] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 20 FN2O2Se + :527.0669,found 527.0656.

[0090] Example 7

[0091]

[0092] 2-(p-Chloro)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ga,E / Z=26 / 74)

[0093] The product 3ga is a yellow solid with a yield of 93% and a melting point (mp): 167.9-168.8°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0094] 1 H NMR (400MHz, CDCl3) δ9.55 (s, 0.26H), 9.38 (s, 0.74H), 8.41-8.38 (m, 1H), 7.86-7.80 (m, 1H), 7.76 (d, J = 8.4Hz, 1H) ,7.60-7.44(m,3H),7.37(t,J=7.6Hz,1H),7.28-7.11(m,9H),6.90(d,J=7.2Hz,1.48H),6.84(d,J=8.4Hz,0.52H).

[0095] 13C NMR (100MHz, CDCl3) δ189.2,188.5,161.1,160.2,153.4,153.1,147.0,1 46.9,142.6,138.1,136.5,136.3,136.2,135.3,134.9,134.3,133.6,133 .5,132.6,131.0,130.2,130.0,129.8,129.6,129.5,129.2,128.9,128. 8,128.6,128.5,128.4,128.1,128.0,127.9,127.8,127.7,120.5,120.3.

[0096] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 20 ClN2O2Se + :543.0373,found 543.0377.

[0097] Example 8

[0098]

[0099] 2-(p-Bromo)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ha,E / Z=38 / 62)

[0100] The product 3ha is a yellow solid with a yield of 94% and a melting point (mp): 158.4-159.1°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0101] 1 H NMR (400MHz, CDCl3) δ9.54 (s, 0.38H), 9.37 (s, 0.62H), 8.41-8.37 (m, 1H), 7.85-8.37 (m, 1H), 7.76 (d, J=8.0Hz, 1 H),7.59-7.53(m,2H),7.45-7.18(m,9H),7.15-7.11(m,2H),6.90(d,J=7.2Hz,1.24H),6.84(d,J=7.6Hz,0.76H).

[0102] 13C NMR (100MHz, CDCl3) δ189.2,188.5,161.1,160.2,153.4,153.2,153.1,147.0, 146.9,142.6,138.1,136.2,135.3,134.9,134.7,134.0,133.5,132.6,131.7, 131.4,131.3,131.0,130.2,130.0,129.9,129.7,129.6,129.3,129.0,128.8,128.6,128.2,128.1,128.0,127.9,127.8,127.7,124.8,124.6,120.5,120.3.

[0103] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 20 BrN2O2Se + :586.9868, found 586.9894.

[0104] Example 9

[0105]

[0106] 2-(p-Trifluoromethyl)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazoli n-4(3H)-one(3ia,E / Z=86 / 14)

[0107] The product is a yellow solid substance 3ia, with a yield of 98% and a melting point (mp): 195.5-196.3°C; its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0108] 1 H NMR (400MHz, CDCl3) δ9.54 (s, 0.86H), 9.36 (s, 0.14H), 8.43-8.39 (m, 1H), 7.83 (ddd, J = 8.0, 7.6, 1.2Hz, 1H), 7. 77(d,J=7.6Hz,1H),7.61-7.33(m,8H),7.25-7.07(m,5H),6.85(d,J=7.6Hz,0.28H),6.79(d,J=7.6Hz,1.72H).

[0109] 13C NMR (100MHz, CDCl3) δ189.3,188.4,161.0,160.0,153.1,152.8,146.9,146.8,141.9,139.2,136.1,135.4,134.9,133.6,132.8,131.9(q, 2 J=32.5Hz),131.8,131.1,130.2,129.9,129.6,129.3,129.0,128.9,12 8.8,128.7,128.6,128.4,128.2,128.1,128.0,127.9,127.8,125.1(q, 3 J=3.6Hz),123.7(q, 1 J=270.9Hz),120.7,120.4.

[0110] 19 F NMR (376MHz, CDCl3) δ-62.88,-62.97.

[0111] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 20 F3N2O2Se + :577.0637,found 577.0637.

[0112] Example 10

[0113]

[0114] 2-(m-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ja,E / Z=92 / 8)

[0115] The product 3ja is a yellow solid with a yield of 96% and a melting point (mp): 122.3-123.3°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0116] 1H NMR (400MHz, CDCl3) δ9.61 (s, 0.92H), 9.36 (s, 0.08H), 8.44-8.39 (m, 1H), 7.83-7.77 (m, 2H), 7.56 (t, J = 7.6Hz, 1H), 7.43-7.41 (m, 2H) ,7.25-7.06(m,9H),6.95(s,0.92H),6.90(s,0.08H),6.84(J=7.6Hz,0.16H),6.80(J=7.6Hz,1.84H),2.21(s,2.76),2.15(s,0.24H).

[0117] 13 C NMR (100MHz, CDCl3) δ188.9,188.6,161.4,160.5,154.6,154.5,154.0,147.2,147.1 ,144.6,138.2,138.1,137.8,136.5,135.6,135.3,135.2,135.1,134.9,133.4,132.2 ,131.6,130.9,130.7,130.1,129.9,129.5,129.2,129.0,128.9,128.8,128.6,128.5,128.1,128.0,127.9,127.8,127.7,127.6,125.3,125.1,120.6,120.2,21.2,21.1.

[0118] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 23 N2O2Se + :523.0919, found 523.0906.

[0119] Embodiment 11

[0120]

[0121] 2-(m-Methoxy)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ka,E / Z=94 / 6)

[0122] The product 3ka is a yellow solid with a yield of 97% and a melting point (mp): 61.2-62.0°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0123] 1 1H NMR (400 MHz, CDCl3) δ 9.60 (s, 0.94H), 9.35 (s, 0.06H), 8.40 (d, J = 7.6 Hz, 1H), 7.84 - 7.77 (m, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.46 - 7.44 (m, 2H), 7.258 - 7.15 (m, 5H), 7.12 - 7.8 (m, 2H), 6.92 (dd, J = 8.4, 2.0 Hz, 1H), 6.88 (d, J = 7.2 Hz, 1H), 6.83 (d, J = 7.6 Hz, 2H), 6.77 (s, 1H), 3.63 (s, 2.82H), 3.61 (s, 0.18H).

[0124] 13 13C NMR (100 MHz, CDCl3) δ 189.0, 188.5, 161.3, 160.3, 159.4, 159.3, 154.2, 154.1, 153.4, 147.1, 147.0, 144.0, 138.1, 136.8, 136.5, 136.1, 135.3, 135.2, 135.1, 133.6, 132.3, 131.4, 130.8, 130.1, 130.0, 129.6, 129.4, 129.3, 129.2, 129.0, 128.9, 128.7, 128.2, 128.0, 127.9, 127.8, 127.7, 120.7, 120.4, 120.3, 116.8, 113.1, 113.0, 55.4.

[0125] HRMS (ESI): m / z [M + H] + calcd for C 30 H 23 N2O3Se + : 539.0868, found 539.0854.

[0126] Example 12

[0127]

[0128] 2-(m-Fluoro)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one (3la, E / Z = 45 / 55)

[0129] The product 3la is a yellow solid with a yield of 98% and a melting point (mp): 62.5-63.3°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0130] 1 H NMR (400MHz, CDCl3) δ9.56 (s, 0.45H), 9.38 (s, 0.55H), 8.41 (t, J = 8.0Hz, 1H), 7.86-7.81 (m, 1H), 7.77 (d, J = 7.6Hz, 1H), 7.5 9-7.56(m,2H),7.46(d,J=7.6Hz,1H),7.37(t,J=8.0,0.55H).7.26-7.18(m,5.45H),7.13-6.91(m,4H),6.89-6.83(m,2H).

[0131] 13 C NMR (100MHz, CDCl3) δ189.3,188.5,162.3(d, 1 J=246.3Hz),162.2(d, 1 J=247.1Hz),161.1,160.2,153.2,153.0(d, 4 J=2.8Hz),152.8(d, 4 J=2.5Hz),146.9,146.8,142.6,138.1,137.6(d, 3 J=7.9Hz),136.9(d, 3 J=7.7Hz),136.2,135.3,134.9,133.5,132.4,131.6,131.0,130.2,130.1,130.0,129.9,129.7 ,129.3,128.9,128.8,128.7,128.1,128.0,127.96,127.91,127.90,127.86,127.81,124.2(d, 3 J=3.2Hz),123.9(d, 3 J=3.1Hz),120.6,120.3,117.3(d, 2 J=21.0Hz),117.1(d, 2 J=21.1Hz),115.7(d, 2 J=23.4Hz),115.6(d, 2 J=23.2Hz).

[0132] 19F NMR (376MHz, CDCl3) δ-111.54,-112.01.

[0133] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 20 FN2O2Se + :527.0669,found 527.0656.

[0134] Example 13

[0135]

[0136] 2-(m-Chloro)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ma,E / Z=62 / 38)

[0137] The product 3ma is a yellow solid with a yield of 97% and a melting point (mp): 67.2-68.1°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0138] 1 H NMR(400MHz, CDCl3)δ9.55(s,0.62H),9.39(s,0.38H),8.43-8.38(m,1H),7.86-7.76(m,2H) ,7.60-7.45(m,3H),7.40-7.10(m,10H),6.88(d,J=7.6Hz,0.76H),6.84(d,J=7.6Hz,1.24H).

[0139] 13 C NMR (100MHz, CDCl3) δ189.3,188.4,161.1,160.2,153.1,153.0,152.7,146.9,146.8,1 42.3,138.1,137.4,136.6,136.2,135.4,135.3,134.9,134.3,134.2,133.5,132.4,131 .7,131.0,130.3,130.2,130.1,130.0,129.7,129.6,129.5,129.3,128.9,128.8,128.7,128.6,128.4,128.2,128.1,128.0,127.9,127.8,127.7,126.5,126.2,120.6,120.4.

[0140] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 20 ClN2O2Se + :543.0373,found 543.0377.

[0141] Embodiment 14

[0142]

[0143] 2-(o-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3na,E / Z=86 / 14)

[0144] The product 3na is a yellow solid with a yield of 90% and a melting point (mp): 81.5-82.4°C; its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0145] 1 H NMR (400MHz, CDCl3) δ9.59 (s, 0.86H), 9.25 (s, 0.14H), 8.50 (d, J = 8.0Hz, 0.14H), 8.44 (d, J = 8.0Hz, 0.86H), 7.86-7. 75(m,2H),7.64-7.46(m,4H),7.32-7.24(m,6H),7.11-7.08(m,2H),6.93(s,1H),6.75(d,J=6.4Hz,2H),1.48(s,3H).

[0146] 13 C NMR (100 MHz, CDCl3) δ 189.1, 188.4, 161.7, 147.1, 147.0, 135.2, 134.3, 133.3, 132.3, 130.8, 130.4, 130.1, 129.9, 129.5, 129.2, 129.0, 128.8, 128.3, 127.9, 127.8, 127.7, 127.6, 125.4, 120.5, 31.5, 30.2. (impure)

[0147] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 23 N2O2Se + :523.0919, found 523.0906.

[0148] Embodiment 15

[0149]

[0150] 2-Thiophen-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3oa,E / Z=65 / 35)

[0151] The product 3oa is a yellow solid with a yield of 94% and a melting point (mp): 61.4-62.3°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0152] 1 H NMR (400MHz, CDCl3) δ9.56 (s, 0.65H), 9.53 (s, 0.35H), 8.32 (d, J = 8.0Hz, 0.65H), 8 .17(d,J=8.0Hz,0.35H),7.81-7.71(m,2H),7.53-7.13(m,12H),7.05-6.94(m,2H).

[0153] 13 C NMR (100MHz, CDCl3) δ189.0,188.3,161.5,160.5,152.5,148.5,147.7,147.3,147 .2,144.9,138.8,137.2,136.7,135.8,135.3,135.1,134.9,134.4,133.3,132.9, 131.0,130.8,130.5,130.3,130.1,129.5,129.2,129.0,128.9,128.7,128.3,128.2,128.0,127.9,127.7,127.6,127.5,127.4,127.3,127.2,126.7,120.2,120.1.

[0154] HRMS(ESI):m / z[M+H] + Calculate for C 27 H 19 N2O2SSe + :515.0327,found 515.0318.

[0155] Example 16

[0156]

[0157] 2-Pyridin-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3pa,E / Z=49 / 51)

[0158] The product 3pa is a yellow solid with a yield of 88% and a melting point (mp): 58.3-59.2°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0159] 1 H NMR (400MHz, CDCl3) δ9.54 (s, 0.49H), 9.38 (s, 0.51H), 8.61-8.52 (m, 2H), 8.41-8.36 (m, 1H), 7.85 (t, J = 7.6Hz, 1H), 7.77 (d,J=8.0Hz,1H),7.65-7.55(m,3H),7.49-7.47(m,1H),7.40-7.11(m,7H),6.94(d,J=7.6Hz,1H),6.83(d,J=7.6Hz,1H).

[0160] 13 C NMR (100MHz, CDCl3) δ189.2,188.4,161.0,160.1,152.3,151.9,151.6,150.9,150 .6,148.8,148.7,146.9,146.8,141.7,138.6,136.1,135.6,135.4,135.3,134.9, 133.8,132.7,132.3,132.1,131.3,131.2,130.3,129.8,129.7,129.2,129.0,128.9,128.4,128.3,128.2,128.0,127.9,127.8,127.5,122.8,122.7,120.6,120.3.

[0161] HRMS(ESI):m / z[M+H] + Calculate for C 28 H 20 N3O2Se + :510.0715, found 510.0732.

[0162] Embodiment 17

[0163]

[0164] 2-Phenyl-7-methyl-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3qa,E / Z=36 / 64)

[0165] The product 3qa is a yellow solid with a yield of 97% and a melting point (mp): 73.4-74.2°C. Its NMR and mass spectrometry experimental data are as follows:

[0166] 1 H NMR (400MHz, CDCl3) δ9.63 (s, 0.36H), 9.35 (s, 0.64H), 8.30 (t, J = 8.4Hz, 1H), 7.60-7.58 (m,2H),7.45-7.15(m,12H),7.06(t,J=7.6Hz,1H),6.83-6.76(m,2H),2.53-2.52(m,3H).

[0167] 13 C NMR (100MHz, CDCl3) δ188.8,188.6,161.3,160.3,154.5,154.3,153.9,147. 3,147.2,146.5,146.4,144.6,137.9,136.5,135.9,135.3,135.1,133.3,13 2.3,131.7,130.8,130.1,130.0,129.9,129.5,129.2,128.9,128.6,128.3,128.2,128.1,128.0,127.9,127.8,127.7,127.6,118.1,117.7,26.9,22.1.

[0168] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 23 N2O2Se + :523.0919, found 523.0906.

[0169] Embodiment 18

[0170]

[0171] 2-Phenyl-6-methoxy-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ra,E / Z=76 / 24)

[0172] The product 3ra is a yellow solid with a yield of 95% and a melting point (mp): 75.5-76.3°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0173] 1 H NMR (400MHz, CDCl3) δ9.62 (s, 1H), 9.36 (s, 1H), 7.79-7.77 (m, 1H), 7.71 (d, J = 8.8Hz, 1H),7.60-7.16(m,12H),7.07(t,J=7.6Hz,2H),6.84-6.77(m,2H),3.96-3.95(m,3H).

[0174] 13 C NMR (100MHz, CDCl3) δ188.8,188.6,161.3,160.2,159.1,154.0,152.1,151.9,14 4.8,141.8,141.7,137.9,136.4,135.8,135.2,135.0,133.3,132.3,131.8,130.8 ,130.0,129.9,129.8,129.6,129.5,129.2,129.1,128.9,128.6,128.5,128.4,128.2,127.9,127.8,127.7,125.5,125.3,121.4,121.0,107.3,107.2,56.0,55.9.

[0175] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 23 N2O3Se + :539.0868, found 539.0854.

[0176] Embodiment 19

[0177]

[0178] 2-Phenyl-6-fluoro-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-on e(3sa,E / Z=39 / 61)

[0179] The product 3sa is a yellow solid with a yield of 84% and a melting point (mp): 64.1-64.9°C. Its NMR and mass spectrometry experimental data are as follows:

[0180] 1 H NMR (400MHz, CDCl3) δ9.56 (s, 0.39H), 9.33 (s, 0.61H), 8.03 (dt, J=8.0, 2.8Hz, 1H), 7.79 (dd, J=8 .8,4.8Hz,1H),7.59-7.51(m,2H),7.44-7.18(m,11H),7.09(t,J=8.0Hz,1H),6.85-6.78(m,2H).

[0181] 13 C NMR (100MHz, CDCl3) δ189.0,188.5,161.3(d, 1 J=248.2Hz),160.7(d, 4 J=3.3Hz),159.7(d, 4 J=3.4Hz),153.7(d, 4 J=2.2Hz),153.6(d, 4 J=2.2Hz),153.2,143.9,143.8,143.4,138.2,136.2,135.5,134.9,134.8,133.6,132.5,131.8,130.9,130.5,13 0.4,130.3,130.2,130.1,129.9,129.6,129.3,128.9,128.7,128.4,128.3,128.2,128.1,128.0,127.9,123.7(d, 2 J=23.8Hz),123.6(d, 2 J=24.0Hz),121.9(d, 3 J=8.7Hz),121.6(d, 3 J=8.7Hz),112.7(d, 2 J=23.7Hz),112.6(d, 3 J=23.7Hz).

[0182] 19 F NMR (376MHz, CDCl3) δ-111.22,-111.32.

[0183] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 20 FN2O2Se + :527.0669,found 527.0656.

[0184] Embodiment 20

[0185]

[0186] 2-Phenyl-6-chloro-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ta,E / Z=45 / 55)

[0187] The product 3ta is a yellow solid with a yield of 99% and a melting point (mp): 69.7-70.6°C; its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0188] 1 H NMR (400MHz, CDCl3) δ9.55 (s, 0.45H), 9.33 (s, 0.55H), 8.36 (d, J = 1.6Hz, 1H), 7.76-7.70(m,2H),7.60-7.58(m,1H),7.44-7.07(m,12H),6.84-6.78(m,2H).

[0189] 13 C NMR (100MHz, CDCl3) δ189.0,188.5,160.4,159.4,154.6,154.5,153.1,145.7,145 .6,143.2,138.3,136.2,135.6,135.5,134.8,134.7,133.6,133.5,133.4,132.5, 131.8,130.9,130.4,130.2,130.1,129.9,129.7,129.6,129.5,129.3,128.9,128.8,128.7,128.3,128.2,128.1,128.0,127.9,127.8,127.1,127.0,121.6,121.3.

[0190] HRMS(ESI):m / z[M+H]+ Calculate for C 29 H 20 ClN2O2Se + :543.0373,found 543.0377.

[0191] Embodiment 21

[0192]

[0193] 2-Phenyl-6-bromo-3-[3-oxo-1-phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ua,E / Z=64 / 36)

[0194] The product 3ua is a yellow solid with a yield of 98% and a melting point (mp): 74.1-75.0°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0195] 1 H NMR (400MHz, CDCl3) δ9.55 (s, 0.64H), 9.33 (s, 0.36H), 8.53 (d, J = 2.0Hz, 1H), 7 .90-7.86(m,1H),7.64(d,J=8.8Hz,1H),7.59-7.07(m,13H),6.84-6.77(m,2H).

[0196] 13 C NMR (100MHz, CDCl3) δ189.0,188.5,160.3,159.3,154.8,154.6,153.0,146. 0,145.9,143.2,138.3,138.2,136.2,135.5,134.8,133.6,132.5,131.8,130 .9,130.4,130.3,130.2,130.1,129.9,129.8,129.7,129.6,129.3,128.9,128.8,128.7,128.3,128.2,128.1,128.0,127.9,122.0,121.7,121.2,121.1.

[0197] HRMS(ESI):m / z[M+H] + Calculate for C 29 H 20 BrN2O2Se + :586.9868,found 586.9860.

[0198] Embodiment 22

[0199]

[0200] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(p-tolylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ab,E / Z=90 / 10)

[0201] The product 3ab is a yellow solid with a yield of 98% and a melting point (mp): 69.3-70.1°C. Its NMR and mass spectrometry experimental data are as follows:

[0202] 1 H NMR (400MHz, CDCl3) δ9.56 (s, 0.9H), 9.34 (s, 0.1H), 8.36 (dd, J = 16.8, 8.0Hz, 1H), 7.82-7.74 (m, 2H), 7.55-7.51 (m, 1H), 7.32(d,J=8.0Hz,1H),7.22-7.18(m,3H),7.08(dd,J=19.0,8.0Hz,6H),6.83(d,J=7.6Hz,1H),2.36(s,3H),2.29(s,3H).

[0203] 13 C NMR (100MHz, CDCl3) δ189.0,188.9,161.5,154.6,147.3,143.5,140.2,137.9,136.5,135.1,134.1,133.1,13 2.9,132.0,130.3,129.9,129.8,128.9,128.8,128.4,128.0,127.9,127.7,127.4,125.1,120.2,21.5,21.2.

[0204] HRMS(ESI):m / z[M+H] + Calculate for C 31 H 25 N2O2Se + :537.1076,found 537.1072.

[0205] Embodiment 23

[0206]

[0207] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(p-methoxyphenylselanyl)]prop-1-en-1-yl-quinazo lin-4(3H)-one(3ac,E / Z=97 / 3)

[0208] The product 3ac is a yellow solid with a yield of 99% and a melting point (mp): 64.7-65.6°C. Its NMR and mass spectrometry experimental data are as follows:

[0209] 1 H NMR (400MHz, CDCl3) δ9.55 (s, 0.97H), 9.30 (s, 0.03H), 8.37 (d, J = 8.0Hz, 1H), 7.82-7.75 (m, 2H), 7.53 (t, J = 8.0Hz, 1H), 7.37 (d, J = 8.4Hz, 1 H),7.24-7.17(m,3H),7.10(t,J=8.0Hz,2H),7.05(d,J=8.0Hz,2H),6.82(d,J=7.6Hz,2H),6.78(d,J=8.8Hz,2H),3.76(s,1H),2.36(s,1H).

[0210] 13 C NMR (100MHz, CDCl3) δ189.0,161.5,160.4,160.0,159.8,154.6,154.4,152.3,147.3,14 7.2,142.8,140.5,140.2,138.6,136.6,136.5,135.3,135.2,135.1,135.0,133.0,132. 5,132.3,130.6,129.9,129.8,128.9,128.8,128.6,128.4,128.2,127.9,127.8,127.7,127.6,127.5,127.3,120.6,120.2,118.4,117.2,115.2,114.7,55.3,55.2,21.5,21.4.

[0211] HRMS(ESI):m / z[M+H] + Calculate for C 31 H 25 N2O3Se + :553.1025, found 553.1014.

[0212] Embodiment 24

[0213]

[0214] 2-(p-methyl)phenyl-3-[3-oxo-1-phenyl-2-(p-tert-butryphenylselanyl)]prop-1-en-1-yl-quinaz olin-4(3H)-one(3ad,E / Z=90 / 10)

[0215] The product 3ad is a yellow solid with a yield of 88% and a melting point (mp): 67.1-68.0°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0216] 1 H NMR (400MHz, CDCl3) δ9.59 (s, 0.9H), 9.35 (s, 0.1H), 8.39 (d, J = 8.0Hz, 1H), 7.83-7.76 (m, 2H), 7.57-7.52 (m, 1H), 7.35 (d, J = 8. 4Hz,2H),7.26(d,J=8.4Hz,2H),7.21-7.18(m,3H),7.09-7.00(m,4H),6.89-6.80(m,2H),2.36-2.33(m,3H),1.28-1.25(m,9H).

[0217] 13 C NMR (100MHz, CDCl3) δ189.1,188.9,161.5,154.6,151.0,147.3,143.6,140.4,140.2,136.5,135.1,133.8,133.1,132.3,131.9,1 30.7,130.0,129.8,128.9,128.8,128.5,128.4,128.2,128.0,127.8,127.7,127.4,126.6,126.3,125.3,120.2,34.6,31.3,21.5.

[0218] HRMS(ESI):m / z[M+H] + Calculate for C 34 H 31 N2O2Se + :579.1545, found 579.1564.

[0219] Embodiment 25

[0220]

[0221] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(2,4,6-trimethylphenylselanyl)]prop-1-en-1-yl-qui nazolin-4(3H)-one(3ae,E / Z=4 / 96)

[0222] The product 3ae is a yellow solid with a yield of 96% and a melting point (mp): 44.6-45.5°C. Its NMR and mass spectrometry experimental data are as follows:

[0223] 1 H NMR (400MHz, CDCl3) δ9.28 (s, 0.04H), 9.23 (s, 0.96H), 8.35 (d, J = 8.0Hz, 1H), 7.79-7.73 (m, 2H), 7.52-7.48 (m, 1H) ,7.24-7.19(m,3H),7.12-7.05(m,4H),6.92(s,2H),6.76(d,J=7.6Hz,2H),2.51(s,6H),2.36(s,3H),2.24(s,3H).

[0224] 13 C NMR (100MHz, CDCl3) δ189.3,188.0,161.6,160.3,154.8,154.4,147.3,147.2,143.5,1 42.8,140.5,140.1,139.7,139.2,138.8,137.0,136.5,135.9,135.0,134.8,133.2,132 .8,131.9,130.4,129.7,129.4,129.1,128.8,128.7,128.6,128.4,128.3,127.9,127.6,127.3,127.2,126.9,125.1,124.0,120.8,120.3,24.7,24.5,21.5,21.4,21.1,21.0.

[0225] HRMS(ESI):m / z[M+H] + Calculate for C 33 H 29 N2O2Se + :565.1389,found 565.1383.

[0226] Embodiment 26

[0227]

[0228] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(p-fluorophenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3af,E / Z=96 / 4)

[0229] The product 3af is a yellow solid with a yield of 97% and a melting point (mp): 45.2-46.1°C. Its NMR and mass spectrometry experimental data are as follows:

[0230] 1 H NMR (400MHz, CDCl3) δ9.65 (s, 0.96H), 9.31 (s, 0.04H), 8.38 (d, J = 7.6Hz, 1H), 7.84-7.76 (m, 2H), 7.58-7.54 (m, 1H), 7.41-7.38 (m, 2H) ,7.21(t,J=7.6Hz,1H),7.13(d,J=8.0Hz,2H),7.07(dd,J=15.6,8.0Hz,4H),6.90(t,J=8.8Hz,2H),6.76(d,J=7.2Hz,2H),2.35(s,3H).

[0231] 13 C NMR (100MHz, CDCl3) δ188.7,188.3,162.5(d, 1 J=246.5Hz),161.6,161.5,161.3,154.5,154.3,153.6,147.3,147.2,145.6,140.6,140.4,138.0,136.4,136.3(d, 3 J=8.0Hz),135.3,135.2,135.0,134.8(d, 3 J=8.0Hz),132.9,132.4,132.3,130.9,130.1,130.0,128.9,128.6,128.3,128.1,128.0,127.9(d, 2 J=25.1Hz),127.8,127.6,127.5,123.6(d, 4 J=3.2Hz),120.5,120.0,116.5(d, 2 J=21.6Hz),116.2(d, 2 J=20.0Hz),21.5,21.4.

[0232] 19F NMR (376MHz, CDCl3) δ-113.49,-113.50.

[0233] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 22 FN2O2Se + :541.0825, found 541.0826.

[0234] Embodiment 27

[0235]

[0236] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(p-chlorophenylselanyl)]prop-1-en-1-yl-quinazoli n-4(3H)-one(3ag,E / Z=53 / 47)

[0237] The product 3ag is a yellow solid with a yield of 81% and a melting point (mp): 79.7-80.5°C. Its NMR and mass spectrometry experimental data are as follows:

[0238] 1 H NMR (400MHz, CDCl3) δ9.66 (s, 0.53H), 9.33 (s, 0.47H), 8.38 (t, J = 8.4Hz, 1H), 7.84-7.76 (m, 2H), 7.58-7.50 (m, 2H),7.37-7.34(m,2H),7.24-7.01(m,9H),6.89(d,J=7.6Hz,1H),6.75(d,J=7.2Hz,1H),2.34(d,J=6.4Hz,3H).

[0239] 13 C NMR (100MHz, CDCl3) δ188.5,188.1,161.5,160.5,154.4,154.3,154.2,147.2,1 47.1,146.5,140.6,140.4,137.6,136.4,135.4,135.3,134.9,134.3,133.8,13 3.7,132.9,132.3,131.9,131.0,130.2,130.0,129.5,129.3,128.9,128.7,128.3,128.1,128.0,127.9,127.8,127.7,127.6,126.4,120.4,119.9,21.5,21.4.

[0240] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 22 ClN2O2Se + :557.0530,found 557.0534.

[0241] Embodiment 28

[0242]

[0243] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(p-bromophenylselanyl)]prop-1-en-1-yl-quinazoli n-4(3H)-one(3ah,E / Z=98 / 2)

[0244] The product 3ah is a yellow solid with a yield of 77% (E / Z=98:2) and a melting point (mp): 75.3-76.2°C. Its NMR and mass spectrometry experimental data are as follows:

[0245] 1 H NMR (400MHz, CDCl3) δ9.67 (s, 0.98H), 9.34 (s, 0.02H), 8.39 (d, J = 7.2Hz, 1H), 7.85-7.81 (m, 1H), 7.78 (d, J = 7.6Hz, 1H), 7.59 -7.55(m,1H),7.30(q,J=8.8Hz,4H),7.22(t,J=7.6Hz,1H),7.09(dt,J=23.2,8.0Hz,6H),6.74(d,J=7.6Hz,2H),2.35(s,3H).

[0246] 13C NMR (100MHz, CDCl3) δ188.5,188.1,161.5,160.5,154.5,154.4,154.2,147.2,147. 1,146.7,140.6,140.4,137.4,136.4,135.4,135.3,135.1,135.0,133.9,132.9,13 2.4,132.3,132.2,131.8,131.0,130.2,130.0,128.9,128.7,128.4,128.2,128.1,128.0,127.9,127.8,127.7,127.6,127.2,122.5,121.9,120.4,119.9,21.5,21.4.

[0247] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 22 BrN2O2Se + :601.0024,found 601.0031.

[0248] Embodiment 29

[0249]

[0250] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(p-trifluoromethylphenylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3ai,E / Z=93 / 7)

[0251] The product 3ai is a yellow solid with a yield of 82% and a melting point (mp): 73.2-74.1°C. Its NMR and mass spectrometry experimental data are as follows:

[0252] 1 H NMR (400MHz, CDCl3) δ9.74 (s, 0.93H), 9.39 (d, 0.07H), 8.42 (d, J = 8.0Hz, 1H), 7.87-7.83 (m, 1H), 7.79 (d, J = 7.6Hz, 1H ),7.62-7.52(m,3H),7.48-7.43(m,2H),7.21(t,J=7.6Hz,1H),7.13-7.04(m,6H),6.72(d,J=7.2Hz,2H),2.36(s,3H).

[0253] 13C NMR (100MHz, CDCl3) δ188.3,187.7,161.6,154.3,148.5,147.1,140.6,136.7,136.3,135.5,135.4,135.0,132.9,132.5,132. 4,131.5,131.3,131.2,130.3,130.1,129.4,129.0,128.9,128.7,128.2,128.1,128.0,127.9,127.8,127.7,126.0,126.0(q, 3 J=3.7Hz),124.0(q, 1 J=271.0Hz),119.8,21.5.

[0254] 19 F NMR (376MHz, CDCl3) δ-62.66,-62.71.

[0255] HRMS(ESI):m / z[M+H] + Calculate for C 31 H 22 F3N2O2Se + :591.0793,found 591.0805.

[0256] Embodiment 30

[0257]

[0258] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(methylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-one(3aj,E / Z=96 / 4)

[0259] The product 3aj is a yellow solid with a yield of 70% and a melting point (mp): 158.2-158.9°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0260] 1H NMR (400MHz, CDCl3) δ9.80 (s, 0.96H), 9.36 (s, 0.04H), 8.36 (d, J = 8.0Hz, 1H), 7.85-7.77 (m, 2H), 7.58-7.54 (m, 1H) ,7.25(t,J=7.6Hz,1H),7.16-7.11(m,4H),7.04(d,J=8.0Hz,2H),6.87(d,J=7.6Hz,2H),2.34(s,1H),2.08(s,1H).

[0261] 13 C NMR (100MHz, CDCl3) δ188.3,161.7,154.6,147.2,146.5,140.4,136.6,135.3,1 33.0,132.7,130.0,128.9,128.8,128.2,128.0,128.0,127.7,119.9,21.4,8.2.

[0262] HRMS(ESI):m / z[M+H] + Calculate for C 25 H 21 N2O2Se + :461.0763, found 461.0764.

[0263] Embodiment 31

[0264]

[0265] 2-(p-Methyl)phenyl-3-[3-oxo-1-phenyl-2-(ethylselanyl)]prop-1-en-1-yl-quinazolin-4(3H)-on e(3ak,E / Z=98 / 2)

[0266] The product 3ak is a yellow solid with a yield of 72% and a melting point (mp): 107.5-108.3°C. Its NMR and mass spectrometry experimental data are as follows:

[0267] 1H NMR (400MHz, CDCl3) δ9.85 (s, 0.98H), 9.42 (s, 0.02H), 8.38 (dd, J=8.0, 0.8Hz, 1H), 7.85-7.77 (m, 2H), 7.56 (td, J=8.0, 1.2Hz, 1H), 7.23 (t, J=7.6 Hz,1H),7.12-7.08(m,4H),7.04(d,J=8.0Hz,2H),6.81(d,J=7.2Hz,2H), 2.88-2.80(m,1H),2.69-2.61(m,1H),2.34(s,3H),1.34(t,J=7.6Hz,3H).

[0268] 13 C NMR (100MHz, CDCl3) δ188.7,161.7,154.6,147.2,146.7,140.4,136.6,135.3,132.8,1 31.8,129.8,129.0,128.9,128.2,128.0,127.9,127.8,127.7,119.9,21.7,21.4,15.8.

[0269] HRMS(ESI):m / z[M+H] + Calculate for C 26 H 23 N2O2Se + :475.0919, found 475.0921.

[0270] Embodiment 32

[0271]

[0272] 2-(p-Methyl)phenyl-3-[3-oxo-1-(p-methoxy)phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quina zolin-4(3H)-one(3wa,E / Z=87 / 13)

[0273] The product 3wa is a yellow solid with a yield of 84% and a melting point (mp): 73.5-75.8°C. Its NMR and mass spectrometry experimental data are as follows:

[0274] 1H NMR (400MHz, CDCl3) δ9.59 (s, 0.87H), 9.35 (s, 0.13H), 8.38-8.35 (m, 1H), 7.79-7.76 (m, 2H), 7.52 (ddd, J = 8.0, 5.2, 2.4Hz, 1H), 7.39-7. 37(m,2H),7.20-7.16(m,5H),7.06(d,J=8.0Hz,2H),6.84(d,J=8.4Hz,2H),6.62(d,J=8.8Hz,2H),3.75-3.71(m,3H),2.34-2.31(m,3H).

[0275] 13 C NMR (100MHz, CDCl3) δ188.7,161.9,161.5,161.1,154.7,147.3,146.1,140.2,135.2,134.8,133.2,133.0,132.0,131.9,13 0.8,130.0,129.7,129.4,129.1,128.9,128.8,128.2,128.1,128.0,127.7,127.5,127.4,120.2,114.2,113.4,55.4,21.5.

[0276] HRMS(ESI):m / z[M+H] + Calculate for C 31 H 25 N2O3Se + :553.1025, found 553.1027.

[0277] Embodiment 33

[0278]

[0279] 2-(p-Methyl)phenyl-3-[3-oxo-1-(p-methyl)phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazo lin-4(3H)-one(3va,E / Z=80 / 20)

[0280] The product 3va is a yellow solid with a yield of 99% and a melting point (mp): 74.3-76.6°C. Its NMR and mass spectrometry experimental data are as follows:

[0281] 1H NMR(400MHz, CDCl3)δ9.58(s,0.8H),9.35(s,0.2H),8.39-8.35(m,1H),7.81- 7.76(m,2H),7.54-7.38(m,3H),7.24-7.15(m,5H),7.06(d,J=8.0Hz,1.6H),7 .02-7.00(m,0.8H),6.90(d,J=8.0Hz,1.6H),6.81(d,J=8.0Hz,0.4H),6.76(d ,J=8.0Hz,1.6H),2.35(s,2.4H),2.32(s,0.6H),2.30(s,0.6H)2.25(s,2.4H).

[0282] 13 C NMR (100MHz, CDCl3) δ188.7,161.5,160.6,154.7,154.4,147.3,145.6,141. 6,140.7,140.4,140.2,137.0,135.1,135.1,133.7,133.3,133.0,132.4,13 2.2,131.9,130.1,129.5,129.4,129.3,129.1,129.0,128.8,128.7,128.4,128.2,128.0,127.9,127.8,127.7,127.6,127.5,127.4,120.5,120.3,21.5.

[0283] HRMS(ESI):m / z[M+H] + Calculate for C 31 H 25 N2O2Se + :537.1076, found 537.1078.

[0284] Embodiment 34

[0285]

[0286] 2-(p-Methyl)phenyl-3-[3-oxo-1-(p-chloro)phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazol in-4(3H)-one(3xa,E / Z=79 / 21)

[0287] The product 3xa is a yellow solid with a yield of 93% and a melting point (mp): 78.6-80.1°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0288] 1 H NMR (400MHz, CDCl3) δ9.59 (s, 0.79H), 9.32 (s, 0.21H), 8.37 (dd, J = 8.4, 1.2Hz, 1H), 7.82-7.75 (m, 2H), 7.57-7.38 (m, 3H) ,7.22-7.17(m,5H),7.10-7.03(m,4H),6.82(d,J=8.8,0.42H),6.73((d,J=8.8,1.58H),2.36(s,2.37H),2.34(s,0.63H).

[0289] 13 C NMR (100MHz, CDCl3) δ188.6,188.2,161.4,160.5,154.2,154.1,147.3,147.2 ,143.2,140.7,140.6,138.7,137.0,135.9,135.3,135.2,135.0,133.8,133.7 ,132.9,132.5,132.2,131.1,130.2,129.5,129.2,128.9,128.9,128.8,128.4,128.2,128.0,127.9,127.8,127.7,127.6,127.5,120.4,120.1,21.5,21.4.

[0290] HRMS(ESI):m / z[M+Na] + Calculate for C 30 H 21 ClN2NaO2Se + :579.0349,found 579.0349.

[0291] Embodiment 35

[0292]

[0293] 2-(p-Methyl)phenyl-3-[3-oxo-1-(p-bromo)phenyl-2-(phenylselanyl)]prop-1-en-1-yl-quinazo lin-4(3H)-one(3ya,E / Z=96 / 4)

[0294] The product 3ya is a yellow solid with a yield of 99% (E / Z=96:4) and a melting point (mp): 82.5-83.8°C. Its nuclear magnetic resonance and mass spectrometry experimental data are as follows:

[0295] 1 H NMR (400MHz, CDCl3) δ9.59 (s, 0.96H), 9.31 (s, 0.04H), 8.37 (dd, J = 8.0, 0.8Hz, 1H), 7.83-7.76 (m, 2H), 7.54 (td, J =8.0,1.2Hz,1H),7.40-7.38(m,2H),7.23-7.19(m,7H),7.09(d,J=8.0Hz,2H),6.66(d,J=8.8Hz,2H),2.37(s,3H).

[0296] 13 C NMR (100MHz, CDCl3) δ188.6,171.1,161.4,154.2,147.1,143.3,140.6,135.4,135.3,132.8,13 2.5,131.1,130.3,129.5,129.0,128.8,128.4,128.0,127.9,127.7,127.6,124.4,120.0,21.5.

[0297] HRMS(ESI):m / z[M+H] + Calculate for C 30 H 22 BrN2O2Se + :601.0024,found 601.0024.

[0298] The above is only a preferred embodiment of the present invention. The present invention is not limited to the above implementation. As long as the technical effect of the present invention is achieved by the same means, it should belong to the protection scope of the present invention. Within the protection scope of the present invention, its technical scheme and / or implementation method can have various modifications and changes.

Claims

1. A method for preparing N-(2-organoselenyl)acrylquinazolinone, comprising the following steps: Under the action of an oxidant, the aryl propargyl quinazoline ether shown in Formula 1 and the diaryl diselenide or dialkyl diselenide shown in Formula 2 react in a solvent to obtain an N-(2-organoselenyl)acryl quinazoline ketone shown in Formula 3; in, R 1 is an aromatic substituent or heteroaryl group containing an electron donating group or an electron withdrawing group; R 2 is H, an electron donating group or an electron withdrawing group; R 3 is an aromatic substituent containing an electron donating group or an electron withdrawing group; R 4 is an alkyl group or an aromatic substituent containing an electron donating group or an electron withdrawing group; The electron-donating group is a C1-C8 alkyl group or a C1-C8 alkoxy group; the electron-withdrawing group is a halogen group or a trifluoromethyl group; the heteroaryl group is a pyridyl group, a thienyl group or a furyl group; The oxidant is tert-butyl hydroperoxide.

2. The method according to claim 1, characterized in that: The electron donating group is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, and ethoxy; the electron withdrawing group is selected from fluorine, chlorine, bromine, iodine, or trifluoromethyl; the aromatic substituent is selected from phenyl, naphthyl, anthracenyl, and phenanthryl; the heteroaryl is selected from pyridyl, thienyl, and furyl.

3. The method according to claim 1, characterized in that: The R 1 is selected from phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, p-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, m-methylphenyl, m-methoxyphenyl, 3-fluorophenyl, 3-chlorophenyl, o-methylphenyl, thienyl, and pyridyl; said R 2 is selected from hydrogen, methyl, methoxy, fluorine, chlorine, and bromine; said R 3 is selected from phenyl, p-methoxyphenyl, p-methylphenyl, 4-chlorophenyl, 4-bromophenyl; said R 4 Selected from phenyl, p-methylphenyl, p-methoxyphenyl, p-tert-butylphenyl, 2,4,6-trimethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, methyl and ethyl.

4. The method according to claim 1, characterized in that: The molar ratio of the aryl propargyl quinazoline ether to the diaryl diselenide or dialkyl diselenide is 1:1-2; the molar ratio of the aryl propargyl quinazoline ether to the oxidant is 1:1-3.

5. The method according to claim 1, characterized in that: The solvent is acetonitrile.

6. The method according to claim 1, characterized in that: The reaction is carried out at 50°C to 70°C.

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