Deuterated quinoxalinone diaryl methane compound as well as synthesis method and application thereof

Abstract

The invention relates to the technical field of organic synthesis, in particular to a deuterated quinoxalinone diaryl methane compound as well as a synthesis method and application thereof. According to the invention, hydrogen transfer of quinoxalinone N = Csp2-H and proton coupling electron transfer of p-methenone are induced by bromine free radicals, and a free radical-free radical cross coupling pathway is established between imine free radicals and diaryl methane free radicals, so that a series of quinoxalinone diaryl methane intermediates are synthesized; and carrying out selective H / D exchange on the site of a tert-benzyl C-H bond of the intermediate through a bromine free radical to obtain a series of highly deuterated quinoxalinone diaryl methane derivatives. A one-pot method is adopted to continuously construct a carbon-carbon bond and a carbon-deuterium bond, the deuterated quinoxalinone diaryl methane derivative which has potential drug activity and can be used for preparing antitumor drugs is obtained, the advantages of high reaction efficiency and atom and step economy are manifested, and the problems of metal residues and the like caused by the use of a transition metal catalyst are avoided.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to deuterated quinoxalinone diarylmethane compounds and a synthesis method and application thereof. Background Art

[0002] Quinoxalinone is a common nitrogen-containing heterocycle and a pharmacophore of many biologically active compounds. The derivatives synthesized with it as the structural nucleus can be used as enzyme inhibitors, γ-aminobutyric acid (GABA) / benzodiazepine receptor antagonists, etc. The synthesized quinoxalinone has important medicinal value. In addition, diarylmethane derivatives are also widely present in biologically active compounds such as drugs and natural products. Among them, the anti-tumor activity of heterocyclized diarylmethane is particularly noteworthy. For example, the triazole diarylmethane derivative letrozole can reduce estrogen levels by inhibiting aromatase, thereby eliminating the stimulating effect of estrogen on tumor growth and is used in the treatment of breast cancer. The construction of a hybrid system with multiple biological and pharmaceutical activities has received widespread attention from medicinal chemists. Therefore, combining the diarylmethane unit with the quinoxalinone skeleton to assemble the heterocyclized diarylmethane skeleton will have attractive potential application value and provide possibilities for drug discovery.

[0003] Deuterium-labeled molecules are widely used in drug metabolism, life sciences, mechanism research, mass spectrometry testing, and development of deuterated drugs. In 2017, the U.S. FDA approved the first deuterated drug, deuterated benzazine, for marketing. Since then, the introduction of deuterium atoms into organic molecules, especially parent drugs and candidate drugs, has attracted widespread attention. If the two active drug skeletons of quinoxalone and diarylmethane can be quickly assembled with deuterium through a one-pot method, it will undoubtedly have important potential medicinal value. The introduction of deuterium will enhance the metabolic stability of the compound, thereby improving the efficacy and reducing the potential toxicity, and thus provide more possibilities for the development of heterocyclic diarylmethane drugs. However, there are no related reports at present.

[0004] Compared with reductive deuteration, defunctionalization, or multi-step synthesis of deuterium-labeled precursors, direct hydrogen / deuterium exchange is the most efficient and economical method for synthesizing deuterium-labeled compounds. Since the 20th century, hydrogen / deuterium exchange induced by expensive metal catalysts or strong bases / strong acids has been well established. However, due to the harsh reaction conditions, the inherent limitations of these closed-shell strategies have affected their practicality and potential in the late functionalization of complex drugs and natural products. It was not until 2017 that the MacMillan group achieved a milestone work on the application of free radical hydrogen isotope exchange (HIE) in complex drugs or drug candidates using a mild, controllable, green and economical visible light catalytic strategy. At present, reports on free radical H / D exchange have developed to α-amino C sp 3-H key, distal C sp 3 -H bond, formyl C sp 2 -H bonds, and silicon-hydrogen bonds, and the benzyl C sp 3 Reports on the HIE of benzylic C-H bonds, especially those of sterically hindered benzyl groups and related drug molecules are rare. For example, MacMillan and Wu reported the HIE of benzylic C-H bonds in the presence of deuterium oxide over sterically hindered thiol HAT catalysts with malodorous properties using photoredox catalysts or HAT-type photocatalysts, respectively. Moderate deuterium incorporation at the benzylic position can be obtained by these methods, but other aliphatic hydrogen atoms at the α position of the heteroatom as well as formyl hydrogen atoms are inevitably exchanged. These pioneering works demonstrated the potential of free radical H / D exchange for the late-stage modification of structurally complex molecules. However, there is still a large gap in improving the catalytic selectivity, efficiency and substrate scope, and it remains to be demonstrated in the deuteration of sterically hindered benzylic C-H bonds and related drugs and natural products. Summary of the invention

[0005] In view of this, the purpose of the present invention is to provide deuterated quinoxalinone diarylmethane compounds and synthesis methods and applications thereof, so as to at least solve the problem of limitations of deuteration of sterically hindered benzyl CH bonds and related drugs and natural products in the prior art, and at the same time provide a synthesis scheme and application of deuterated quinoxalinone diarylmethane derivatives with important potential medicinal value.

[0006] The present invention solves the above technical problems by the following technical means:

[0007] In a first aspect, an embodiment of the present invention provides a deuterated quinoxalinone diarylmethane compound having the following general structural formula:

[0008]

[0009] Among them, R 1 is alkyl, aryl or heteroaryl; R 2 is hydrogen, alkyl, halogen, or aryl; R 3 is an alkyl group; Ar is a substituted or unsubstituted aryl group.

[0010] In a second aspect, the present invention also provides a method for synthesizing a deuterated quinoxalinone diarylmethane compound, wherein the method uses an organic photocatalyst Mes-Acr + ClO4 -As an electron transfer catalyst, NBS as a hydrogen atom transfer catalyst, D2O as a deuterium source, methyl quinone compound b and quinoxalinone compound a as main reaction raw materials, under blue light irradiation, react at room temperature to prepare deuterated quinoxalinone diarylmethane compounds. The general reaction formula of the synthesis method is as follows:

[0011]

[0012] Among them, R 1 is alkyl, aryl or heteroaryl; R 2 is hydrogen, alkyl, halogen, or aryl; R 3 is an alkyl group; Ar is a substituted or unsubstituted aryl group.

[0013] In a third aspect, an embodiment of the present invention further provides the use of the deuterated quinoxalinone diarylmethane compounds described in the first aspect or the deuterated quinoxalinone diarylmethane compounds synthesized by the synthesis method described in the second aspect in the preparation of anti-tumor drugs, wherein the anti-tumor drugs are used to treat prostate cancer or pancreatic cancer.

[0014] The present invention utilizes organic photocatalyst Mes-Acr + ClO4 - As an electron transfer catalyst, NBS as a HAT catalyst, and D2O as a cheap deuterium source, a site-selective reductive coupling and deuteration reaction of p-methyl quinone (p-QMs) with quinoxaline-2(1H)-one was developed in a metal-free manner with extremely high reaction efficiency. sp 2 The reaction proceeds through HAT of -H and proton-coupled electron transfer of p-methylquinone, establishing a radical-radical cross-coupling pathway between imine radicals and diarylmethane radicals to synthesize a series of quinoxalinone diarylmethane intermediates, followed by site-selective H / D exchange of the tertiary benzyl CH bond of the intermediates by bromine radicals to obtain a series of highly deuterated quinoxalinone diarylmethane derivatives. The reaction achieves excellent D-introduction (up to 96%) at the predicted sites even in substrates containing more than one reactive CH bond or multifunctional functional groups. The free radical hydrogen-deuterium exchange work first constructed quinoxalinone diarylmethane through the reductive coupling of quinoxalinone and p-methenquinone, and then exchanged the tert-benzyl hydrogen-deuterium of quinoxalinone diarylmethane with bromine radical. These two consecutive steps quickly constructed important deuterated quinoxalinone diarylmethane derivatives in one pot, demonstrating the advantages of high reaction efficiency and atom and step economy, and realizing efficient and site-selective free radical hydrogen-deuterium exchange of sterically hindered benzyl CH bonds and related drugs and natural products.

[0015] The synthesis method of the invention is simple, efficient, and mild, and at the same time avoids residues of transition metals and the like, and has the characteristics of being green and environmentally friendly; it utilizes visible light and bromine free radicals to synergistically catalyze a tandem reaction, and has the advantages of atomic and step economy and high chemical selectivity; it obtains high-value-added heterocyclic molecules from simple and readily available raw materials, and has a low synthesis cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is the general structural formula of the deuterated quinoxalinone diarylmethane compound of the present invention;

[0017] Figure 2 The general reaction formula involved in the synthesis method of the deuterated quinoxalinone diarylmethane compounds of the present invention is:

[0018] Figure 3 It is an organic photocatalyst Mes-Acr + ClO4 - Chemical structure of

[0019] Figure 4 is the reaction mechanism involved in the synthesis method of the present invention;

[0020] Figure 5 and 6 It is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-methylquinoxalin-2(1H)-one 1 H NMR and 13 C NMR spectra; Figure 7 and 8 It is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(3-hydroxy-4-methoxyphenyl)methyl-d)-1-methylquinoxalin-2(1H)-one 1 H NMR and 13 C NMR spectra; Fig. 9 and 10 It is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(4-(phenylthio)phenyl)methyl-d)-1-methylquinoxalin-2(1H)-one 1 H NMR and 13 C NMR spectra; Fig.11 , 12 and 13 are 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(4-(trifluoromethyl)phenyl)methyl-d)-1-methylquinoxalin-2(1H)-one 1 H NMR, 13 C NMR and 19 F NMR spectra; Fig.14 , 15and 16 are 3-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-fluorobenzyl)-6,7-dimethylquinoxalin-2(1H)-one 1 H NMR and 13 C NMR spectra; Fig.17 and 18 It is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-methyl-5,6-diphenylpyrazin-2(1H)-one 1 HNMR and 13 C NMR; Fig.19 and 20 It is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-((2-oxo-2H-chromen-7-yl)oxy)propyl)quinoxalin-2(1H)-one 1 H NMR and 13 C NMR spectra; Fig.21 and 22 It is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl)oxy)propyl)quinoxalin-2(1H)-one 1 H NMR and 13 C NMR spectra; Fig.23 and 24 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-(2-isopropyl-5-methylphenoxy)propyl)quinoxaline-2-yl

[0021] (1H)-Keto 1 H NMR and 13 C NMR spectra; Fig.25 and 26 It is 2-(3-((3,5-di-tert-butyl-4-hydroxyphenyl)

[0022] (phenyl)methyl-d)-2-oxoquinoxalin-1(2H)-yl)ethyl (2R)-2-(4-isobutylphenyl)propanoate 1 H NMR and 13 C NMR spectra; Fig. 27 and 28 2-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxalin-1(2H)-yl)ethyl-6-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)-2-naphthoate 1H NMR and 13 C NMR spectra; Fig.29 , 30 and 31 are ethyl 2-(3-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxalin-1(2H)-yl)-3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoate 1 H NMR, 13 C NMR and 19 F NMR spectrum. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0024] The English letters in the present invention are defined as follows: HAT: hydrogen atom transfer; NBS: N-bromosuccinimide; TFA: trifluoroacetic acid; EA: ethyl acetate; p-QM: p-methenequinone; PCET: proton-coupled electron transfer.

[0025] The structural formula of the deuterated quinoxalinone diarylmethane compound of the present invention is as follows Figure 1 As shown. Among them, R 1 is an alkyl, aryl or heteroaryl group, R 2 is hydrogen, alkyl, halogen, or aryl; R 3 is an alkyl group; Ar is a substituted or unsubstituted aryl group. In some embodiments, R 1 methyl, 3-fluorobenzyl, 3-((2-oxo-2H-chromen-7-yl)oxy)propyl, (3-((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl)oxy)propyl, 3-(2-isopropyl-5-methylphenoxy)propyl, ethyl (2R )-2-(4-isobutylphenyl)propionate, ethyl-6-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)-2-naphthoate or ethyl 3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoate; Ar is selected from phenyl, 3-hydroxy-4-methoxyphenyl, 4-(phenylthio)phenyl, 4-(trifluoromethyl)phenyl or naphthalene-2-yl; R 2 is hydrogen; R 3 It is tert-butyl.

[0026] The synthesis method of deuterated quinoxalinone diarylmethane compounds of the present invention utilizes organic photocatalyst Mes-Acr + ClO4 - As an electron transfer catalyst, NBS as a hydrogen atom transfer catalyst, D2O as a deuterium source, methyl quinone compound b and quinoxalinone compound a as the main reaction raw materials, under blue light irradiation, the deuterated quinoxalinone diarylmethane compound is prepared by reaction at room temperature. The general reaction formula involved is as follows: Figure 2 As shown. Among them, the molar ratio of quinoxaline compound a to methenylquinone compound b is 1:1.5, the molar ratio of quinoxaline compound a to NBS is 1:0.4, and the molar ratio of quinoxaline compound a to organic photocatalyst Mes-Acr + ClO4 - The molar ratio of is 1:0.02, and the molar ratio of quinoxalinone compound a to D2O is 1:20. The blue light irradiation is irradiated by a blue light emitting diode with a power of 8 to 12 W and a wavelength of 430-460 nm, preferably 10 W and a wavelength of 454 nm; the reaction time at room temperature is 10 to 15 hours, preferably 12 hours.

[0027] The reaction mechanism involved in the synthesis method of the present invention is as follows Figure 4 As shown in the figure, the catalytic amount of NBS (BDE = 58.0 kcal / mol) directly undergoes N-Br bond homolysis through visible light photolysis (470 nm blue photon energy = 60.7 kcal / mol), thereby obtaining bromine radicals and starting the entire catalytic process. The bromine radicals required to maintain the entire catalytic cycle are achieved through the photocatalytic single-electron oxidation of bromine anions. The excited photocatalyst Mes-Acr + ClO4 - It is a strong oxidizing agent that can achieve Br - The single electron oxidation of bromine free radicals. The transient bromine free radicals from the N = C sp 2 -H bond, selectively extracting hydrogen atoms to generate imine radical I and release HBr. + will participate in the formation of p-QM b with H-bond complex II, promoting electron transfer in the reduced form of the photocatalyst to generate diarylmethyl radical III. Radical III can then combine with radical I to generate coupling product c. In the deuteration reaction, the Br radical generated by the second photoredox cycle is converted from the tertiary benzyl C sp 3 -H selectively extracts a hydrogen atom from the tertiary benzyl radical IV and releases HBr. + Rapidly exchanges H with D2O to form D+ , D + is the source of deuterium. On the other hand, free radical IV then reduces the photosensitizer [Mes-Acr + ] - accepts an electron to generate an anion V, which can react with D + A deuteration reaction occurs to generate a deuterated product 1.

[0028] The deuterated quinoxalinone diarylmethane compounds in Examples 1-12 were synthesized using the following synthesis method:

[0029] Quinoxalinone a (0.1 mmol, 1 eq) was added to NBS (0.04 mmol, 0.4 eq, 7 mg), b (0.15 mmol, 1.5 eq), D2O (2 mmol, 20 eq, 36 μl) and Mes-Ac in a glass vial equipped with a magnetic stir bar and a nitrogen inlet. + ClO4 - The mixture was added with 1-(4-(2-nitropropene)-2-nitropropene (0.002 mmol, 2 mol%, 1.3 mg) dry DCM (1 ml), the mixture was purged by evacuating the glass bottle three times and backfilling with nitrogen, and then placed in an irradiation device equipped with a 10 W blue light emitting diode (LED) strip (with a wavelength of 454 nm) for blue light irradiation. The reaction was stirred at room temperature for 12 hours. The crude product obtained by the reaction was purified by column chromatography (silica gel, EtOAc:n-Hexane=1:10~1:5) to obtain the desired product 1-12.

[0030] Example 1

[0031] The compound synthesized in this example is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-methylquinoxaline-2(1H)-one. In this example, R 1 is methyl, R 2 is hydrogen, R 3 The synthesis method of the deuterated quinoxalinone diarylmethane compound of this embodiment is as described above. The synthesized deuterated quinoxalinone diarylmethane compound 1 is a yellow oil with a yield of 95% ( 1 H NMR D incorporation rate: 93%). 1 H NMR and 13 C NMR images Figure 5 and 6 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0032] 1H NMR(400MHz, CDCl3)δ7.84(dd,J=7.9,1.3Hz,1H),7.53–7.39(m,5H),7.32–7.24(m,3H),7.1 8(ddd,J=9.0,5.9,2.2Hz,2H),6.24(s,0.07H),5.09(s,1H),3.64(s,3H),1.40(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ161.1,154.8,152.7,142.3,135.4,133.0,132.7,131.2,130.3,129.9,129 .2,128.3,126.5,126.4,123.5,113.5,51.5-50.9(m),34.5,30.5,30.4,29.4ppm; HRMS(ESI)m / z calcd for C 30 H 34 DN2O2 + (M+H) + 456.2756, found m / z 456.2753.

[0033] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 1 of this example is inferred to be as follows:

[0034]

[0035] Example 2

[0036] The compound synthesized in this example is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(3-hydroxy-4-methoxyphenyl)methyl-d)-1-methylquinoxaline-2(1H)-one. In this example, R 1 is methyl, R 2 is hydrogen, R 3 is tert-butyl, and Ar is 3-hydroxy-4-methoxyphenyl. The synthesis method of the deuterated quinoxalinone diarylmethane compound of this embodiment is as described above. The synthesized deuterated quinoxalinone diarylmethane compound 2 is a yellow solid with a yield of 78% ( 1 H NMR D incorporation rate: 91%). 1 H NMR and 13 C NMR Figure 7 and 8 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0037] 1H NMR (400MHz, CDCl3) δ7.89–7.79(m,1H),7.55–7.46(m,1H),7.40(d,J=3.8Hz,2H),7.28(ddd,J=10.3,9.0,5.0Hz,2H),7.08(dd,J=3.7,2.0Hz,1 H),6.96(ddd,J=8.2,3.9,2.0Hz,1H),6.87–6.75(m,1H),6.15(s,0.09H ),5.51(s,1H),5.08(s,1H),3.84(s,3H),3.67(s,3H),1.41(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ161.2,154.8,152.6,146.3,144.2,135.3,133.9,133.0,132.7,131.5,130.2 ,129.9,126.3,123.5,121.9,114.0,113.5,112.1,55.8,51.0,34.4,30.4,29.4ppm; HRMS(ESI)m / z calcd for C 31 H 36 DN2O4 + (M+H) + 502.2811, found m / z 502.2811.

[0038] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 2 of this example is inferred to be as follows:

[0039]

[0040] Example 3

[0041] The compound synthesized in this example is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(4-(phenylthio)phenyl)methyl-d)-1-methylquinoxaline-2(1H)-one. In this example, R 1 is methyl, R 2 is hydrogen, R 3 The synthesis method of the deuterated quinoxalinone diarylmethane compound of this embodiment is as described above. The synthesized deuterated quinoxalinone diarylmethane compound 3 is a yellow solid with a yield of 87% ( 1 H NMR D incorporation rate: 91%). 1 H NMR and 13 C NMR Fig. 9 and 10As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0042] 1 H NMR(400MHz, CDCl3)δ7.84(dd,J=8.0,1.3Hz,1H),7.53–7.46(m,1H),7.45–7.38(m,4H),7.33–7.28(m,3H),7.2 7–7.21(m,5H),7.18(ddd,J=7.0,3.7,1.3Hz,1H),6.21(s,0.09H),5.10(s,1H),3.67(s,3H),1.40(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ160.7,154.8,152.7,141.5,136.2,135.5,133.2,133.0,132.7,131.2,130.9,130.7, 130.3,130.0,130.0,129.1,126.8,126.4,123.5,113.5,51.0-50.4(m),34.4,30.4,29.4ppm; HRMS(ESI)m / z calcd for C 36 H 38 DN2O2S + (M+H) + 564.2790, found m / z 564.2797.

[0043] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 3 of this example is inferred to be as follows:

[0044]

[0045] Example 4

[0046] The compound synthesized in this example is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(4-(trifluoromethyl)phenyl)methyl-d)-1-methylquinoxaline-2(1H)-one. In this example, R 1 is methyl, R 2 is hydrogen, R 3 is tert-butyl, Ar is 4-(trifluoromethyl)phenyl. The synthesis method of this embodiment is as described above, and the synthesized deuterated quinoxalinone diarylmethane compound 4 is a yellow solid with a yield of 88% ( 1 H NMR D incorporation rate: 92%). 1 H NMR, 13 C NMR and 19 F NMR Fig.11 , 12 As shown in Figure 13, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0047] 1 H NMR (400MHz, CDCl3) δ7.85 (dd, J=8.0, 1.2Hz, 1H), 7.60–7.49 (m, 5H), 7.41 (s, 2H), 7.37–7.3 0(m,1H),7.28(d,J=8.4Hz,1H),6.28(s,0.08H),5.13(s,1H),3.68(s,3H),1.41(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ160.3,154.7,152.9,146.4,135.7,133.0,132.6,130.3,130.2,129.4,129.0,128.5 (q, J=32. 2Hz),128.1,126.4,125.2,125.1,124.0,123.7(q,J=280.7Hz),123.7,113.6,51.3-50.7(m),34.5,30.3,29.5ppm; 19 F NMR(376MHz, CDCl3)δ-62.29(s)ppm; HRMS(ESI)m / z calcd for C 31 H 33 DF3N2O2 + (M+H) + 524.2630, found m / z 524.2635.

[0048] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 4 of this example is inferred to be as follows:

[0049]

[0050] Example 5

[0051] The compound synthesized in this example is 3-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-fluorobenzyl)-6,7-dimethylquinoxaline-2(1H)-one. In this example, R 1 is 3-fluorobenzyl, R 2 is 6,7-dimethyl, R 3 is tert-butyl, Ar is phenyl. The synthesis method of this embodiment is as described above, and the synthesized deuterated quinoxalinone diarylmethane compound 5 is a yellow solid with a yield of 82% ( 1H NMR D incorporation rate: 91%). 1 H NMR, 13 C NMR and 19 F NMR Fig.14 , 15 As shown in Figure 16, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0052] 1 H NMR (400MHz, CDCl3) δ7.62(s,1H),7.47(d,J=7.1Hz,2H),7.41(d,J=4.6Hz,2H),7.28(t,J=7.5Hz,2H),7.22(ddd,J=21.4,9.8,4.7H z,2H),6.91(ddd,J=21.2,15.5,8.8Hz,4H),6.23(s,0.09H),5.42(s,2H),5.09(s,1H),2.29(s,3H),2.28(s,3H),1.41(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ164.4,161.9,159.9,154.8,152.6,142.4,139.8,13 8.2(d,J=7.3Hz),135.4,132.7,132.0–131.1(m),130.7,130.5(d,J=8.4Hz ),130.2,129.2,128.3,126.4(d,J=2.9Hz),122.4(d,J=2.9Hz),114.7,11 4.5,113.9(d,J=22.0Hz),51.8-51.2(m),45.6,34.5,30.4,20.6,19.2ppm; 19 F NMR (376MHz, CDCl3) δδ-112.11 (dd, J=15.3, 8.5Hz) ppm; HRMS (ESI) m / z calcd for C 38 H 41 DFN2O2 + (M+H) + 578.3288, found m / z 578.3286.

[0053] The structure of the product was determined by X-ray single crystal diffraction, and its CCDC number is: 2377163. Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 5 of this example is inferred to be as follows:

[0054]

[0055] Example 6

[0056] The compound synthesized in this example is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-methyl-5,6-diphenylpyrazine-2(1H)-one. In this example, R 1 is methyl, R 2 is 5,6-diphenyl, R 3 The synthesis method of the deuterated quinoxalinone diarylmethane compound of this embodiment is as described above. The synthesized deuterated quinoxalinone diarylmethane compound 6 is a yellow solid with a yield of 73% ( 1 H NMR D incorporation rate: 91%). 1 H NMR and 13 C NMR Fig.17 and 18 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0057] 1 H NMR (400MHz, CDCl3) δ7.62–7.57(m,2H),7.52(s,2H),7.39(dd,J=9.7,6.5Hz,4H),7.32–7.25(m,3H) ,7.18–7.12(m,3H),7.12–7.07(m,3H),6.19(s,0.09H),5.08(s,1H),3.27(s,3H),1.40(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ157.7,155.5,152.6,142.6,138.0,136.5,135.3,132.8,132.2,132.0,131.9,130.2,130.1,129.6,129.5,129.3, 129.3,129.2,129.1,128.8,128.5,128.3,128.3,127.5,126.7,126.6,126.3,51.2-50.6(m),34.5,34.4,30.4,30.3ppm; HRMS(ESI)m / z calcd for C 38 H 40 DN2O2 + (M+H) + 558.3225, found m / z 558.3229.

[0058] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 6 of this example is inferred to be as follows:

[0059]

[0060] Example 7

[0061] The compound synthesized in this example is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-((2-oxo-2H-chromen-7-yl)oxy)propyl)quinoxaline-2(1H)-one. In this example, R 1 is 3-((2-oxo-2H-chromen-7-yl)oxy)propyl, R 2 is hydrogen, R 3 is tert-butyl, Ar is phenyl. The synthesis method of this embodiment is as described above, and the synthesized deuterated quinoxalinone diarylmethane compound 7 is a yellow solid with a yield of 64% ( 1 H NMR D incorporation rate: 88%). 1 H NMR and 13 C NMR images Fig.19 and 20 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0062] 1 H NMR(400MHz, CDCl3)δ7.96(d,J=8.2Hz,1H),7.76(d,J=8.2Hz,1H),7.66–7.56(m,2H) ,7.55–7.43(m,1H),7.39–7.27(m,5H),7.25–7.14(m,3H),6.75(dd,J=8.6,2.3Hz,1H) ,6.71(d,J=2.2Hz,1H),6.25(d,J=9.5Hz,1H),5.92(s,0.12H),5.10(s,1H),4.63(dd ,J=8.0,3.6Hz,2H),3.91(dd,J=7.8,4.4Hz,2H),2.36–2.03(m,2H),1.37(s,18H)ppm; 13CNMR (100MHz, CDCl3) δ162.0,161.3,155.8,155.4,152.6,151.4,143.4,142.4,139.6,138.6,135.4,131.2,129.3,129.0,128.7 ,128.3,126.6,126.4,126.4,126.4,113.2,112.9,112.6,101.6,65.0,62.8,53.1-52.4(m),34.4,30.4,29.7ppm; HRMS(ESI)m / z calcdfor C 41 H 42 DN2O5 + (M+H) + 644.3229, found m / z 644.3233.

[0063] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 7 of this example is inferred to be as follows:

[0064]

[0065] Example 8

[0066] The compound synthesized in this embodiment is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl)oxy)propyl)quinoxaline-2(1H)-one. In this embodiment, R 1 is (3-((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl)oxy)propyl, R 2 is hydrogen, R 3 is tert-butyl, Ar is phenyl. The synthesis method of this embodiment is as described above, and the synthesized deuterated quinoxalinone diarylmethane compound 8 is a yellow solid with a yield of 54% ( 1 H NMR D incorporation rate: 90%). 1 H NMR and 13 C NMR images Fig.21 and 22 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0067] 1H NMR(400MHz, CDCl3)δ7.87(d,J=7.8Hz,1H),7.52–7.39(m,6H),7.29(dd,J=15.5,7.9Hz,3H),7.24 –7.12(m,2H),6.72(dd,J=8.5,2.3Hz,1H),6.65(s,1H),6.24(s,0.1H),5.09(s,1H),4.49–4.31(m, 2H),4.04(t,J=5.6Hz,2H),3.08–2.82(m,2H),2.51(dd,J=18.8,8.5Hz,1H),2.40(d,J=9.5Hz,1H), 2.31–1.89(m,8H),1.57(dd,J=18.6,8.3Hz,2H),1.41(s,18H),1.39–1.36(m,3H),0.91(s,3H)ppm; 13 C NMR (100MHz, CDCl3) δ160.9,156.7,154.6,152.6,142.3,137.9,135.4,133.0, 132.5,132.2,131.3,130.5,130.0,129.1,128.3,126.5,126.4,123.4,114.6,1 13.6,112.3,65.3,51.3-50.8(m),50.5,48.1,44.0,40.2,38.4,35.9,34.5,31. 6,31.5,30.4,30.2,29.7,29.7,27.3,26.6,26.0,21.6,13.9ppm; HRMS(ESI)m / z calcd for C 50 H 58 DN2O4 + (M+H) + 752.4532, found m / z 752.4539.

[0068] It should be noted that the carbonyl carbon chemical shift (about 220 ppm) of the compound 4Ga in this example exceeds the detection range of the NMR instrument, so no peak is observed. Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 8 in this example is inferred as follows:

[0069]

[0070] Example 9

[0071] The compound synthesized in this embodiment is 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-(2-isopropyl-5-methylphenoxy)propyl)quinoxaline-2(1H)-one. In this embodiment, R 1 is 3-(2-isopropyl-5-methylphenoxy)propyl, R 2 is hydrogen, R 3 The synthesis method of the deuterated quinoxalinone diarylmethane compound of this embodiment is as described above. The synthesized deuterated quinoxalinone diarylmethane compound 9 is a yellow solid with a yield of 85% ( 1 H NMR D incorporation rate: 91%). 1 H NMR and 13 C NMR images Fig.23 and 24 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0072] 1 H NMR (400MHz, CDCl3) δ7.88 (d, J=7.8Hz, 1H), 7.54–7.43 (m, 6H), 7.34–7.24 (m, 3H), 7.22–7 .15(m,1H),7.12(d,J=7.7Hz,1H),6.77(d,J=7.7Hz,1H),6.64(s,1H),6.25(s,0.09H),5. 10(s,1H),4.47(dd,J=8.7,6.1Hz,2H),4.08(t,J=5.6Hz,2H),3.37(dt,J=13.8,6.9Hz,1H ),2.30(s,3H),2.25(dt,J=12.5,5.9Hz,2H),1.42(s,18H),1.27(s,3H),1.26(s,3H)ppm; 13 C NMR (100MHz, CDCl3) δ161.0,155.6,154.6,152.7,142.3,136.6,135.4,133.8,133.0,132.2,131.3,130.6,130.0,129.1,128.3,126 .5,126.4,125.9,123.5,121.6,113.5,112.2,65.2,51.4-50.7(m),40.3,34.5,30.4,27.4,26.8,23.0,22.9,21.4ppm; HRMS(ESI)m / z calcd for C 42 H 50 DN2O3 +(M+H) + 632.3957, found m / z 632.3959.

[0073] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 9 of this example is inferred to be as follows:

[0074]

[0075] Example 10

[0076] The compound synthesized in this example is 2-(3-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxaline-1(2H)-yl)ethyl (2R)-2-(4-isobutylphenyl)propionate. In this example, R 1 is ethyl (2R)-2-(4-isobutylphenyl) propionate, R 2 is hydrogen, R 3 is tert-butyl, Ar is phenyl. The synthesis method of this embodiment is as described above, and the synthesized deuterated quinoxalinone diarylmethane compound 10 is a yellow solid with a yield of 86% ( 1 H NMR D incorporation rate: 92%). 1 H NMR and 13 C NMR Fig.25 and 26 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0077] 1 H NMR (400MHz, CDCl3) δ7.85 (d, J=7.8Hz, 1H), 7.52–7.38 (m, 5H), 7.28 (ddd, J=9.9, 9.0,4.4Hz,4H),7.21–7.14(m,1H),7.05(ddd,J=19.7,8.1,1.8Hz,4H),6.21(s,0 .08H),5.10(s,1H),4.61–4.12(m,4H),3.51(dq,J=14.4,7.2Hz,1H),2.41(d,J=7 .1Hz,2H),1.83(td,J=13.4,6.7Hz,1H),1.41(s,18H),0.88(d,J=6.6Hz,6H)ppm; 13C NMR (100MHz, CDCl3) δ174.7,160.8,154.6,152.6,142.2,140.7,137.3,135.4,135.4,132.9,132.5,132.5,131.2,130.5,129.9,129.4,129.1, 129.1,128.3,127.1,126.4,123.5,113.7,113.6,61.0,61.0,51.4-50. 9(m),45.1,45.0,41.1,34.4,30.4,30.2,22.4,18.3ppm; HRMS(ESI)m / z calcd for C 44 H 52 DN2O4 + (M+H) + 674.4063, found m / z 674.4069.

[0078] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 10 of this example is inferred to be as follows:

[0079]

[0080] Embodiment 11

[0081] The compound synthesized in this example is 2-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxaline-1(2H)-yl)ethyl-6-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)-2-naphthoate. In this example, R 1 is ethyl-6-(3-((3r, 5r, 7r)-adamantan-1-yl)-4-methoxyphenyl)-2-naphthoate, R 2 is hydrogen, R 3 The synthesis method of the deuterated quinoxalinone diarylmethane compound of this embodiment is as described above. The synthesized deuterated quinoxalinone diarylmethane compound 11 is a yellow solid with a yield of 94% ( 1 HNMR D incorporation rate: 91%). 1 H NMR and 13 CNMR Fig. 27 and 28 As shown, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0082] 1H NMR (400MHz, CDCl3) δ8.40(s,1H),7.98(s,1H),7.93–7.88(m,2H),7.83(dd,J=11.5,8. 7Hz,2H),7.77(dd,J=8.5,1.7Hz,1H),7.62–7.42(m,8H),7.37–7.29(m,1H),7.26(t,J=7 .6Hz,2H),7.17(t,J=7.3Hz,1H),6.98(d,J=8.6Hz,1H),6.27(s,0.09H),5.09(s,1H),4 .88–4.43(m,4H),3.89(s,3H),2.18(s,6H),2.10(s,3H),1.80(s,6H),1.41(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ166.7,161.0,159.0,154.7,152.7,142.3,141.6,139.1,136 .1,135.5,133.0,132.7,132.5,131.2,131.1,130.6,130.0,129.7,129.1,128.3, 126.5,126.5,126.4,126.2,126.0,125.8,125.5,124.7,123.6,113.9,112.2,61. 5,55.2,51.3-50.7(m),41.4,40.7,37.3,37.2,34.4,30.4,29.2ppm; HRMS(ESI)m / z calcd forC 59 H 62 DN2O5 + (M+H) + 880.4794, found m / z 880.4792.

[0083] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 11 of this example is inferred to be as follows:

[0084]

[0085] Example 12

[0086] The compound synthesized in this example is ethyl 2-(3-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxaline-1(2H)-yl)-3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoate. In this example, R 1 is ethyl 3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoate, R2 is hydrogen, R 3 The synthesis method of the pyrrolo[1,2-a]quinoxaline-4(5H)-one compound of this embodiment is as described above. The synthesized deuterated quinoxaline ketone diarylmethane compound 12 is a yellow solid with a yield of 90% ( 1 H NMR D incorporation rate: 91%). 1 H NMR, 13 C NMR and 19 F NMR Fig.29 , 30 As shown in Figure 31, the characterization data such as nuclear magnetic resonance and high-resolution mass spectrometry are as follows:

[0087] 1 H NMR(400MHz, CDCl3)δ8.75(t,J=1.5Hz,1H),8.39–8.31(m,1H),8.23(td,J=7.8,1.7Hz,1H),8.07–7.96(m,1H),7.92–7.79(m,1H),7.67– 7.57(m,1H),7.57–7.42(m,7H),7.38–7.23(m,5H),7.21–7.09(m,1H),6.26(s,0.09H),5.10(s,1H),4.87–4.33(m,4H),1.41(s,18H)ppm; 13 C NMR (100MHz, CDCl3) δ173.1 (d, J = 4.4Hz), 167.9, 165.8, 162.1, 160.9, 159.5, 154.7, 152.6, 142.2,135.4,134.8(d,J=8.4Hz),132.9,132.5,132.3,132.0,131.2,131.1,130.6,130.4, 130.2,129.2,129.1,129.1,128.9,128.3,127.3,126.5,126.4,124.9(d,J=3.7Hz),123.7, 117.2(d,J=20.9Hz),113.6,112.7(d,J=11.4Hz),61.8,51.3-50.6(m),41.3,34.4,30.4ppm; 19 F NMR(376MHz, CDCl3)δ-104.13–-112.22(m)ppm; HRMS(ESI)m / z calcd for C 46 H 43 DFN4O5 + (M+H)+ 752.3353, found m / z752.3349.

[0088] Based on the above characterization data, the structure of the deuterated quinoxalinone diarylmethane compound 12 of this example is inferred to be as follows:

[0089]

[0090] Biological activity test: The deuterated quinoxalinone diarylmethane compounds synthesized in Examples 1-12 were tested for antitumor activity. Human prostate cancer cell DU145 and pancreatic cancer cell BxpC3 were selected. These cell lines were purchased from the American Type Culture Collection (ATCC). DU145 was cultured in DMEM medium, and BxpC3 was cultured in RPMI1640 medium. All culture media were supplemented with 10% fetal bovine serum (FBS) to provide growth factors required for cell growth. The cell culture conditions were a constant temperature incubator at 37°C and 5% CO2. The culture steps were as follows:

[0091] (1) Tumor cells in the logarithmic growth phase were digested with trypsin and resuspended in complete medium. The cell concentration was measured using a cell counter and the cells were diluted to 3×10 4 Pieces / mL;

[0092] (2) Inoculate 100 μL of cell suspension in each well of a 96-well plate and incubate overnight in a cell culture incubator;

[0093] (3) Compounds 1-12 were diluted to 20 μM with the complete culture medium of the corresponding cells, and 100 μL of the compound dilution was added to each well of a 96-well plate to make the final concentration of the compound 10 μM. Each compound was added to 3 replicate wells, and the control group was DMSO with an equal volume as the compound. The cells were returned to the cell culture incubator and cultured for 72 hours;

[0094] (4) The inhibitory effect of compounds 1-12 on the survival ability of various tumor cells was detected by MTT assay. After the tumor cells were treated with the compounds for 72 hours, 20 μL of 5 mg / mL MTT solution was added to each well and incubated at 37°C for another 4 hours;

[0095] (5) Discard the cell culture medium, add 150 μL DMSO to dissolve the cells, and measure the OD value at 570 nm (OD570) using a microplate reader;

[0096] (6) Data processing: relative survival rate was calculated based on OD570 of the compound-treated group and the control-treated group. Cell survival rate = OD570 化合物 / OD570DMSO The effects of 10 μM compound 1-12 on the growth ability of prostate cancer cell lines and pancreatic cancer cell lines are shown in Table 1.

[0097] Table 1

[0098]

[0099] The data in Table 1 show that the deuterated quinoxalinone diarylmethane compounds of the present invention can inhibit or kill tumor cells, have anti-tumor activity, and can be used in the preparation of anti-tumor drugs for treating prostate cancer and pancreatic cancer.

[0100] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the purpose and scope of the technical solutions of the present invention, which should be included in the scope of the claims of the present invention. The techniques, shapes, and structural parts not described in detail in the present invention are all known technologies.

Claims

1. A deuterated quinoxalinone diarylmethane compound, characterized in that: It has the following general structural formula: Among them, R 1 is alkyl, aryl or heteroaryl; R 2 is hydrogen, alkyl, halogen, or aryl; R 3 is an alkyl group; Ar is a substituted or unsubstituted aryl group.

2. The deuterated quinoxalinone diarylmethane compound according to claim 1, characterized in that: The R 1 is selected from methyl, 3-((2-oxo-2H-chromen-7-yl)oxy)propyl, (3-((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl)oxy)propyl, 3-(2-isopropyl-5-methylphenoxy)propyl, ethyl (2R)-2-(4-isobutylphenyl)propanoate, ethyl-6-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)-2-naphthoate or ethyl 3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoate; said R 2 is hydrogen; Ar is selected from phenyl, 3-hydroxy-4-methoxyphenyl, 4-(phenylthio)phenyl, 4-(trifluoromethyl)phenyl or naphthalene-2-yl; The R 3 It is tert-butyl.

3. The deuterated quinoxalinone diarylmethane compound according to claim 1, characterized in that: The deuterated quinoxalinone diarylmethane compound is selected from: 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-methylquinoxalin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(3-hydroxy-4-methoxyphenyl)methyl-d)-1-methylquinoxalin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(4-(phenylthio)phenyl)methyl-d)-1-methylquinoxalin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(4-(trifluoromethyl)phenyl)methyl-d)-1-methylquinoxalin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(naphthalen-2-yl)methyl-d)-1-methylquinoxalin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-methyl-5,6-diphenylpyrazin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-((2-oxo-2H-chromen-7-yl)oxy)propyl)quinoxalin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl)oxy)propyl)quinoxalin-2(1H)-one; or, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-1-(3-(2-isopropyl-5-methylphenoxy)propyl)quinoxalin-2(1H)-one; or, 2-(3-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxalin-1(2H)-yl)ethyl (2R)-2-(4-isobutylphenyl)propanoate; or, 2-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxalin-1(2H)-yl)ethyl-6-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)-2-naphthoate; Or, ethyl 2-(3-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl-d)-2-oxoquinoxalin-1(2H)-yl)-3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)benzoate.

4. A method for synthesizing deuterated quinoxalinone diarylmethane compounds, characterized in that: The synthesis method utilizes organic photocatalyst Mes-Acr + ClO4 - As an electron transfer catalyst, NBS as a hydrogen atom transfer catalyst, D2O as a deuterium source, methyl quinone compound b and quinoxalinone compound a as main reaction raw materials, under blue light irradiation, react at room temperature to prepare deuterated quinoxalinone diarylmethane compounds. The general reaction formula of the synthesis method is as follows: Among them, R 1 is alkyl, aryl or heteroaryl; R 2 is hydrogen, alkyl, halogen, or aryl; R 3 is an alkyl group; Ar is a substituted or unsubstituted aryl group.

5. The method for synthesizing deuterated quinoxalinone diarylmethane compounds according to claim 4, characterized in that: The molar ratio of the quinoxaline compound a to the methenol compound b is 1:1.

5.

6. The method for synthesizing deuterated quinoxalinone diarylmethane compounds according to claim 4, characterized in that: The molar ratio of the quinoxalinone compound a to NBS is 1:0.

4.

7. The method for synthesizing deuterated quinoxalinone diarylmethane compounds according to claim 4, characterized in that: The quinoxaline compound a and the organic photocatalyst Mes-Acr + ClO4 - The molar ratio is 1:0.

02.

8. The method for synthesizing deuterated quinoxalinone diarylmethane compounds according to claim 4, characterized in that: The molar ratio of the quinoxalinone compound a to D2O is 1:

20.

9. The method for synthesizing deuterated quinoxalinone diarylmethane compounds according to claim 4, characterized in that: The blue light irradiation is irradiation using a blue light emitting diode with a power of 8 to 12 W and a wavelength of 430 nm to 460 nm, and the room temperature reaction time is 10 to 15 hours.

10. Use of the deuterated quinoxalinone diarylmethane compound according to any one of claims 1 to 3 or the deuterated quinoxalinone diarylmethane compound synthesized by the synthesis method according to any one of claims 4 to 9 in the preparation of an anti-tumor drug, wherein the anti-tumor drug is used to treat prostate cancer or pancreatic cancer.

Images