Preparation method of selenium-containing or sulfur-containing pyrimidine heterocyclic compound

Abstract

The invention provides a preparation method of a selenium-containing or sulfur-containing pyrimidine heterocyclic compound, and belongs to the field of organic synthesis. The invention provides a preparation method of a 2, 4-disubstituted-5-(sulfur / selenium group) pyrimidine compound, which comprises the following steps: mixing an enaminone compound, an amidine compound and an analogue thereof, a sulfuration / selenylation reagent and a polar organic solvent, and carrying out olefin addition and subsequent cyclization reaction to obtain the 2, 4-disubstituted-5-(sulfur / selenium group) pyrimidine compound. The preparation method disclosed by the invention has the advantages of no need of transition metal and other external oxidants, wide substrate range, good functional group tolerance, high regioselectivity, simplicity and convenience in operation, mild conditions and the like, and the prepared 2, 4-disubstituted-5-(thio / seleno) pyrimidine compound has relatively high purity which is 98.5-99.9%.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and particularly to a method for preparing a selenium- or sulfur-containing pyrimidine heterocyclic compound. Background Art

[0002] Among a wide variety of nitrogen-containing heterocyclic compounds, pyrimidine is an important electron-rich aromatic heterocycle and is a key endogenous component of the human body as a building block of DNA and RNA. Selenium- and sulfur-containing pyrimidine heterocyclic compounds also play extremely important roles in life sciences, not only because of their specific affinities for various biological receptors, but also due to their high bio-pharmaceutical activities.

[0003] Currently, the preparation of selenium- and sulfur-containing pyrimidine heterocyclic compounds usually involves 2 - 3 steps using transition metals as catalysts, with cumbersome preparation steps and low purity of the obtained selenium- or sulfur-containing pyrimidine heterocyclic compounds. Summary of the Invention

[0004] The present invention provides a method for preparing a selenium- or sulfur-containing pyrimidine heterocyclic compound, which does not require a transition metal when preparing the selenium- or sulfur-containing pyrimidine heterocyclic compound and has a high purity of the product.

[0005] The present invention provides a method for preparing a selenium- or sulfur-containing pyrimidine heterocyclic compound, and the steps are as follows:

[0006] Mix an amidine compound or 2-aminobenzimidazole with an enaminone compound, a compound having the structural formula shown in Formula IV, and a polar organic solvent, heat them to carry out an olefin addition reaction and a ring-forming reaction, and then purify the obtained product to obtain a selenium- or sulfur-containing pyrimidine heterocyclic compound;

[0007] The selenium- or sulfur-containing pyrimidine heterocyclic compound has the structural formula shown in Formula I;

[0008] The enaminone compound has the structure shown in Formula II:

[0009]

[0010] The amidine compound has the structure shown in Formula III:

[0011]

[0012] R 1 is a first aryl group, a first substituted aryl group, a first heteroaryl group or a first alkyl group; R 2 is a second aryl group, a second substituted aryl group, a second heteroaryl group, a second alkyl group or hydrogen; R 3 is a third aryl group, a third substituted aryl group, a third heteroaryl group or a third alkyl group;

[0013] X is S or Se.

[0014] The present invention uses amidine compounds or 2-aminobenzimidazole, enaminone compounds, compounds with the structural formula shown in Formula IV, and polar organic solvents as raw materials to prepare 2,4-disubstituted-5-(sulfur / selenium-based) pyrimidine compounds. After connecting different substituents to the enaminone compounds, amidine compounds, and compounds with the structural formula shown in Formula IV, they can still well adapt to this reaction, and thio / selenopyrimidine compounds can be obtained by a one-pot method.

[0015] The preparation method of the present invention has the advantages of no need for transition metals and other external oxidants, a broad substrate range, high regioselectivity, mild conditions, simple operation, economical steps, cheap and easily available raw materials, a wide substrate range, good functional group tolerance, and no need for transition metals and other external oxidants. Moreover, the prepared selenium- or sulfur-containing pyrimidine heterocyclic compounds have a high purity, with a purity of 98.5 - 99.9%. Compared with multi-step synthesis reactions, the present invention can obtain the target product by a one-pot method, and the reaction yield can reach 92%, having the advantages of high reaction efficiency and economical steps. Detailed implementation manners

[0016] The present invention provides a method for preparing selenium- or sulfur-containing pyrimidine heterocyclic compounds, including the following steps:

[0017] Mix an amidine compound or 2-aminobenzimidazole with an enaminone compound, a compound with the structural formula shown in Formula IV, and a polar organic solvent and heat them to undergo an olefin addition reaction and a cyclization reaction, and then purify the obtained product to obtain a selenium- or sulfur-containing pyrimidine heterocyclic compound;

[0018] The selenium- or sulfur-containing pyrimidine heterocyclic compound has the structural formula shown in Formula I;

[0019] The enaminone compound has the structure shown in Formula II:

[0020]

[0021] The amidine compound has the structure shown in Formula III:

[0022]

[0023] R 1 is a first aryl group, a first substituted aryl group, a first heteroaryl group, or a first alkyl group; R 2 is a second aryl group, a second substituted aryl group, a second heteroaryl group, a second alkyl group, or hydrogen; R 3 is a third aryl group, a third substituted aryl group, a third heteroaryl group, or a third alkyl group;

[0024] X is S or Se.

[0025] In the present invention, unless otherwise specified, the materials and equipment used are commercially available products in the art.

[0026] In the present invention, the molar ratio of the enaminone compound to the amidine compound or 2-aminobenzimidazole is preferably 1:1 to 3. In specific embodiments of the present invention, the molar ratio of the enaminone compound to the amidine compound or 2-aminobenzimidazole can be 1:1, 1:1.5, 1:2, 1:2.5 or 1:3.

[0027] In the present invention, the enaminone compound has the structure shown in Formula II:

[0028]

[0029] In the present invention, R 1 is a first aryl group, a first substituted aryl group, a first heteroaryl group or a first alkyl group. The first substituted aryl group preferably includes a halophenyl group, a trifluoromethylphenyl group, an alkylphenyl group, an alkoxyphenyl group, a nitrophenyl group, a cyanophenyl group, a vinylphenyl group or a methylenedioxyphenyl group; the alkylphenyl group preferably includes a methylphenyl group; the alkoxyphenyl group preferably includes a methoxyphenyl group or an ethoxyphenyl group.

[0030] The first aryl group preferably includes a phenyl group, a naphthyl group or a biphenyl group.

[0031] The first heteroaryl preferably includes furyl, thienyl, pyridyl or pyrazinyl;

[0032] The first alkyl group preferably includes an isopropyl group or an adamantyl group.

[0033] In the present invention, the enaminoketone compounds preferably include (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, (E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(4-iodophenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(3-methoxyphenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(3-cyanophenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(2-bromophenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(2-methylphenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(3,4-dichlorophenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-naphthalen-2-ylprop-2-en-1-one, (E)-3-(dimethylamino)-1-(6-methoxynaphthalen-2-yl)prop-2-en-1-one, 3-(dimethylamino)-1-biphenylprop-2-en-1-one, (1E,4E)-1-(dimethylamino)penta-1,4-dien-3-one, (E)-3-(dimethylamino)-1-(benzo[d][1,3]dioxol-5-yl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(furan-2-yl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(thiophen-2-yl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(pyridin-4-yl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(pyrazin-2-yl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-isopropylprop-2-en-1-one or (E)-3-(dimethylamino)-1-((3R,5R,7R)-adamantan-1-yl)prop-2-en-1-one.

[0034] In a specific embodiment of the present invention, the enaminone compounds can be referred to as follows: (1) Huo, J.; Geng, X.; Li, W.; Zhang, P.; Wang, L. Photoinduced Three-Component Cyclization of Arylamines, Enaminones and Difluorobromoacetates to 2,3-Difunctionalized Quinolines. Adv. Synth. Catal. 2022, 364, 3539-3543. DOI: 10.1002 / adsc.202200615; (2) Liang X, Guo P, Yang W, Li M; Jiang C; Sun W; Loh T-P; Jiang W. Stereoselective synthesis of trifluoromethyl-substituted 2H-furan-amines from enaminones[J]. Chemical Communications, 2020, 56(13):2043-2046. DOI: 10.1039 / C9CC08582C; (3) Qian, Y.; Schürmann, M.; Janning, P.; Hedberg, C.; Waldmann, H. Activity-Based Proteome Profiling Probes Based on Woodward's Reagent K with Distinct Target Selectivity. Angew. Chem. Int. Ed., 2016, 55, 7766-7771. DOI: 10.1002 / anie.201602666; (4) Stanek, J.; Caravatti, G.; Capraro, H.-G.; Furet, P.; Mett, H.; Schneider, P.; Regenass, U. S-Adenosylmethionine Decarboxylase Inhibitors: New Aryl and Heteroaryl Analogs of Methylglyoxal Bis(guanylhydrazone). J. Med. Chem. 1993, 36, 46-54. DOI: 10.1021 / jm00053a007; (5) Wu, W.; Wu, X.; Fan, S.; Zhu, J.Preparation was carried out according to the content in "Rh(III)-Catalyzed Enaminone-Directed C-H Coupling with Diazodicarbonyls for Skeleton-Divergent Synthesis of Isocoumarins and Naphthalenes. Org. Lett. 2022, 24, 7850-7855. DOI: 10.1021 / acs.orglett.2c03288.".

[0035] In the present invention, the amidine compound has the structure shown in Formula III:

[0036]

[0037] In the present invention, R 2 is a second aryl group, a second substituted aryl group, a second heteroaryl group, a second alkyl group or hydrogen. The second aryl group preferably includes a phenyl group; the second substituted aryl group preferably includes a halophenyl group, an alkylphenyl group or an alkoxyphenyl group; the second heteroaryl group preferably includes a pyridyl group or a pyrazinyl group; the second alkyl group preferably includes a tert-butyl group; the amidine compound preferably includes benzamidine, 4-bromobenzamidine, 4-methoxybenzamidine, 3-bromobenzamidine, 3-methoxybenzamidine, 2-fluorobenzamidine, 2-methylbenzamidine, 3-pyridinecarboxamidine, 4-pyridinecarboxamidine, formamidine or 2,2-dimethylpropanamidine.

[0038] In the present invention, the molar ratio of the enaminone compound to the compound having the structural formula shown in Formula IV is preferably 1:1 to 3. In specific embodiments of the present invention, the molar ratio of the enaminone compound to the compound having the structural formula shown in Formula IV can be 1:1, 1:1.5, 1:2, 1:2.5 or 1:3.

[0039] In the present invention, R 3 is a third aryl group, a third substituted aryl group, a third heteroaryl group or a third alkyl group. The third aryl group preferably includes a phenyl group; the third substituted aryl group preferably includes a halophenyl group, an alkylphenyl group, an alkoxyphenyl group or a benzothiazolyl group; the third heteroaryl group preferably includes a pyridyl group; the third alkyl group preferably includes a methyl group.

[0040] In the present invention, the thio / selenobenzenesulfonate preferably includes S-phenylthiophenesulfonate, S-(p-tolyl)thiophenesulfonate, S-(4-chlorophenyl)thiophenesulfonate, S-(2-fluorophenyl)thiophenesulfonate, S-(2-pyridyl)thiophenesulfonate, S-(2-benzothiazolyl)thiophenesulfonate, Se-phenylthiophenesulfonate, Se-(4-fluorophenyl)thiophenesulfonate, Se-(3,4-dimethoxy)thiophenesulfonate or Se-methylthiophenesulfonate.

[0041] In the present invention, the dosage ratio of the polar organic solvent to the enaminone compound is preferably 1 L: 0.1 - 1 mol, and the dosage ratio of the polar organic solvent to the enaminone compound can be 1 L: 0.1 mol, 1 L: 0.2 mol, 1 L: 0.3 mol, 1 L: 0.4 mol, 1 L: 0.5 mol, 1 L: 0.6 mol, 1 L: 0.7 mol, 1 L: 0.8 mol, 1 L: 0.9 mol or 1 L: 1 mol; the polar organic solvent preferably includes one or more of dimethyl sulfoxide, N,N-dimethylformamide, 1,2-dichloroethane, toluene, acetonitrile, N-methylpyrrolidone and N,N-dimethylacetamide.

[0042] In the present invention, the heating temperature is 60 - 120 °C and the time is 3 - 24 h. In specific embodiments of the present invention, the heating temperature can be 60 °C, 70 °C, 80 °C, 90 °C, 100 °C, 110 °C or 120 °C, and the time can be 3 h, 5 h, 7 h, 9 h, 10 h, 12 h, 15 h, 18 h, 20 h, 22 h or 24 h.

[0043] In the present invention, the heating is preferably carried out under stirring in an oil bath. The present invention has no special requirements for the stirring speed, and a commonly used speed in the art can be adopted to ensure the smooth progress of the reaction. In the present invention, the amidine compound or 2-aminobenzimidazole is mixed with the enaminone compound, the compound having the structural formula shown in Formula IV, and the polar organic solvent. By using the one-pot method, the α-position of the enaminone olefin is first subjected to addition, and then a cycloaddition reaction is carried out to obtain a selenium- or sulfur-containing pyrimidine heterocyclic compound, wherein 2,4-disubstituted pyrimidine is regarded as a by-product in this reaction process. The reaction formula is as follows (1 mL of solvent is relative to 0.1 mmol of enaminone compound):

[0044]

[0045] In the present invention, the purification method is preferably column chromatography, and the eluent used in the column chromatography is preferably a mixed solvent of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 1 to 30:1. In specific embodiments of the present invention, the volume ratio of petroleum ether to ethyl acetate can be 1:1, 10:1, 20:1 or 30:1. The present invention has no special requirements for the specific process of the column chromatography, and the method well-known to those skilled in the art can be adopted. The present invention uses petroleum ether and ethyl acetate as eluents for purification, and the purity of the obtained target compound is relatively high, up to 99.9%.

[0046] The purity of the selenium- or sulfur-containing pyrimidine heterocyclic compound prepared by the preparation method of the present invention is 98.5 to 99.9%; the yield is preferably 23 to 92%.

[0047] In the present invention, the selenium- or sulfur-containing pyrimidine heterocyclic compound preferably has a structural formula shown in any one of Formula I-1 to Formula I-41:

[0048]

[0049]

[0050]

[0051] The selenium- or sulfur-containing pyrimidine heterocyclic compound of the present invention can undergo gram-scale reactions and can also undergo oxidation reactions or Sonogashira coupling reactions to be converted into pharmaceutical and pesticide products.

[0052] The preparation method of the selenium- or sulfur-containing pyrimidine heterocyclic compound provided by the present invention will be described in detail below with reference to the examples, but they should not be construed as limiting the protection scope of the present invention.

[0053] Example 1

[0054] The 2,4-diphenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0055]

[0056] 0.1 mmol of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product, 2,4-diphenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 92% and a purity of 99.9%.

[0057] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0058] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.71(dd, J = 7.8, 1.8 Hz, 2H), 8.65(s, 1H), 8.06(dd, J = 7.6, 2.0 Hz, 2H), 7.58(dq, J = 9.9, 5.1 Hz, 6H), 7.45(dd, J = 7.9, 1.7 Hz, 2H), 7.39 - 7.32(m, 3H).

[0059] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 164.1, 161.7, 159.1, 137.3, 136.8, 132.8, 132.0, 130.5, 129.7, 129.4, 129.2, 128.3, 128.0, 127.9, 127.8.

[0060] MS(EI, 70 eV) m / z 340, 263, 165, 134, 77.

[0061] Example 2

[0062] The 4-(4-fluorophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0063]

[0064] 0.1 mmol of (E)-3-(dimethylamino)-1-(4-fluorophenyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1. The purified target product 4-(4-fluorophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound was obtained with a yield of 81% and a purity of 99.9%.

[0065] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0066] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.58 - 8.48 (m, 3H), 7.96 (dd, J = 8.8, 5.4 Hz, 2H), 7.53 - 7.48 (m, 3H), 7.35 (td, J = 6.6, 6.1, 2.8 Hz, 5H), 7.21 (t, J = 8.7 Hz, 2H).

[0067] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 163.8 (d, J = 250.7 Hz), 163.4, 162.0, 159.6 (d, J = 3.0 Hz), 136.9, 133.5 (d, J = 3.2 Hz), 132.8, 132.1, 131.5 (d, J = 8.5 Hz), 130.8, 129.7, 128.5, 128.3, 128.1, 127.6, 115.2 (d, J = 21.7 Hz).

[0068] MS (EI, 70 eV) m / z 358, 281, 228, 134, 77.

[0069] Example 3

[0070] The 4-(4-iodophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0071]

[0072] 0.1 mmol of (E)-3-(dimethylamino)-1-(4-iodophenyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1. The purified target product, 4-(4-fluorophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 70% and a purity of 99.9%.

[0073] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0074] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.58 - 8.49 (m, 3H), 7.87 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.1 Hz, 2H), 7.50 (dd, J = 3.9, 2.1 Hz, 3H), 7.39 - 7.30 (m, 5H).

[0075] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 163.3, 161.9, 159.5, 137.3, 136.8, 136.7, 132.5, 132.2, 130.9, 130.8, 129.7, 128.5, 128.3, 128.0, 127.7, 96.8.

[0076] MS(EI, 70 eV) m / z 466, 389, 262, 165, 77.

[0077] Example 4

[0078] The 4-(4-trifluoromethylphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0079]

[0080] 0.1 mmol of (E)-3-(dimethylamino)-1-(4-trifluoromethylphenyl)prop-2-en-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product, 4-(4-trifluoromethylphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 65% and a purity of 99.9%.

[0081] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0082] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.60 (s, 1H), 8.57–8.50 (m, 2H), 8.02 (d, J = 8.1 Hz, 2H), 7.79 (d, J = 8.2 Hz, 2H), 7.55 - 7.48 (m, 3H), 7.35 (tt, J = 7.8, 3.6 Hz, 5H).

[0083] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 163.1, 162.2, 159.6, 140.8, 136.7, 132.4, 132.3, 131.6 (d, J = 32.6 Hz), 130.9, 129.73, 129.66, 128.6, 128.4, 128.2, 128.1, 125.1 (q, J = 3.7 Hz), 123.9 (d, J = 272.5 Hz).

[0084] MS (EI, 70 eV) m / z 408, 331, 262, 165, 134.

[0085] Example 5

[0086] The 4-(4-methoxyphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0087]

[0088] Add 0.1 mmol of (E)-3-(dimethylamino)-1-(4-methoxyphenyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 20:1, obtaining the purified target product 4-(4-methoxyphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound with a yield of 85% and a purity of 99.9%;

[0089] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0090] 1 H NMR(400 MHz, CDCl3, ppm) δ8.56 - 8.50(m, 3H), 8.00 - 7.96(m, 2H), 7.52 - 7.48(m, 3H), 7.40 - 7.30(m, 5H), 7.08 - 7.02(m, 2H), 3.89(s, 3H).

[0091] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ163.8, 161.8, 161.1, 159.5(d, J = 3.0 Hz), 137.1, 133.3, 132.1, 131.1, 130.6, 129.9, 129.6, 128.5, 128.1, 128.1, 127.2, 113.6, 55.3(d, J = 4.1 Hz).

[0092] MS(EI, 70 eV) m / z 370, 293, 250, 134, 77.

[0093] Example 6

[0094] The 4-(3-methoxyphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0095]

[0096] 0.1 mmol of (E)-3-(dimethylamino)-1-(3-methoxyphenyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1, obtaining the purified target product 4-(3-methoxyphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound with a yield of 81% and a purity of 99.9%;

[0097] The structure of the obtained product was characterized, and the structure characterization data was as follows:

[0098] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.64 - 8.52(m, 3H), 7.57 - 7.31(m, 11H), 7.09(d, J = 8.0 Hz, 1H), 3.88(s, 3H).

[0099] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 164.0, 161.7, 159.3, 158.99, 158.96, 138.7, 136.9, 132.8, 132.3, 130.6, 129.6, 129.1, 128.4, 128.2, 128.1, 128.0, 121.6, 115.8, 114.5, 55.2.

[0100] MS(EI, 70 eV) m / z 370, 293, 250, 134, 77.

[0101] Example 7

[0102] The 4-(3-cyanophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0103]

[0104] 0.1 mmol (E)-3-(dimethylamino)-1-(3-cyanophenyl)-2-propen-1-one, 0.3 mmol benzamidine, 0.3 mmol S-phenylthiobenzenesulfonate and 1 mL dimethyl sulfoxide were added to a reaction tube and stirred in an oil bath at 110°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate in the eluent was 5:1, and the purified target product 4-(3-cyanophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound was obtained with a yield of 70% and a purity of 99.9%.

[0105] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0106] 1 H NMR (400MHz, CDCl3, ppm) δ8.59(s,1H),8.51-8.46(m,2H),8.20(t,J=1.4Hz,1H),8.13(dt,J=7.9,1.5 Hz,1H),7.76(dt,J=7.8,1.3Hz,1H),7.59(t,J=7.8Hz,1H),7.49(dd,J=6.8,2.9Hz,3H),7.33(s,5H).

[0107] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.3,162.1,159.9,138.5,136.4,133.5,133.0, 132.9,132.1,131.0,129.7,128.9,128.7,128.5,128.1,127.9,118.3,112.4.

[0108] MS(EI,70eV)m / z 365,288,235,134,77.

[0109] Example 8

[0110] The 4-(3-cyanophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0111]

[0112] 0.1 mmol of (E)-3-(dimethylamino)-1-(2-bromophenyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product, 4-(2-bromophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 47% and a purity of 99.9%.

[0113] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0114] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.64(s, 1H), 8.51(dd, J = 6.5, 2.9 Hz, 2H), 7.72(d, J = 8.0 Hz, 1H), 7.56 - 7.45(m, 4H), 7.45 - 7.30(m, 9H).

[0115] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 165.4, 162.1, 158.8, 158.7, 138.6, 136.9, 132.9, 132.5, 132.4, 130.7, 130.4, 130.1, 129.8, 129.5, 128.5, 128.3, 128.2, 127.2, 121.

[0116] MS(EI, 70 eV) m / z 420, 339, 312, 262, 235.

[0117] Example 9

[0118] The 4-(2-methylphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:3]

[0119]

[0120] 0.1 mmol of (E)-3-(dimethylamino)-1-(2-methylphenyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product, 4-(2-methylphenyl)-2-phenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 68% and a purity of 99.9%.

[0121] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0122] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.57(s, 1H), 8.54 - 8.47(m, 2H), 7.52 - 7.47(m, 3H), 7.44–7.32(m, 9H), 2.31(s, 3H).

[0123] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 166.2, 161.7, 157.6, 137.1, 137.0, 135.7, 133.0, 131.9, 130.6, 130.5, 130.1, 129.6, 129.2, 128.6, 128.5, 128.1, 125.6, 19.6.

[0124] MS(EI, 70 eV) m / z 354, 277, 263, 160, 115.

[0125] Example 10

[0126] The 4-(3,4-dichlorophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0127]

[0128] 0.1 mmol of (E)-3-(dimethylamino)-1-(3,4-dichlorophenyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added into a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product 4-(3,4-dichlorophenyl)-2-phenyl-5-(phenylthio)pyrimidine compound was obtained with a yield of 67% and a purity of 99.9%.

[0129] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0130] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.55 (s, 1H), 8.50 (dt, J = 5.0, 3.1 Hz, 2H), 8.03 (d, J = 1.9 Hz, 1H), 7.76 (dd, J = 8.3, 1.9 Hz, 1H), 7.56 (d, J = 8.3 Hz, 1H), 7.52 - 7.48 (m, 3H), 7.38 - 7.31 (m, 5H).

[0131] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 162.1, 161.9, 159.72, 159.69, 137.2, 136.6, 134.2, 132.5, 132.2, 131.3, 130.9, 130.1, 129.7, 128.5, 128.5, 128.1, 127.9.

[0132] MS (EI, 70 eV) m / z 408, 331, 296, 261, 134.

[0133] Example 11

[0134] The 4-(1-naphthyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0135]

[0136] 0.1 mmol of (E)-3-(dimethylamino)-1-(1-naphthyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added into a reaction tube, and stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1, and the purified target product 4-(1-naphthyl)-2-phenyl-5-(phenylthio)pyrimidine compound was obtained with a yield of 73% and a purity of 99.9%;

[0137] The structure of the obtained product was characterized, and the structure characterization data was as follows:

[0138] 1 H NMR(400MHz,CDCl3,ppm)δ8.67(s,1H),8.56(dd,J=6.5,3.0Hz,2H),8.01(dd,J=18.0,7.7Hz,2H),7.79(d,J=8.2Hz,1H),7.67-7.50(m,7H),7.35(dd,J=6.6,3.0Hz,2H),7.32-7.27(m,3H).

[0139] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ165.0,161.7,157.9,136.9,135.0,133.6,133.0,132.0,131.1,130.7,130.5,129.7,129.5,128.5,128.4,128.1,127.0,126.6,126.1,125.1,124.9.

[0140] MS(EI,70eV)m / z 390,313,258,183,151.

[0141] Example 12

[0142] The 4-(6-methoxynaphthalen-2-yl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0143]

[0144] 0.1 mmol of (E)-3-(dimethylamino)-1-(6-methoxynaphthalen-2-yl)prop-2-en-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added into a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1. The purified target product 4-(6-methoxynaphthalen-2-yl)-2-phenyl-5-(phenylthio)pyrimidine compound was obtained with a yield of 84% and a purity of 99.9%.

[0145] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0146] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.63 (dd, J = 7.6, 2.0 Hz, 2H), 8.59 (s, 1H), 8.43 - 8.39 (m, 1H), 8.10 (dd, J = 8.6, 1.7 Hz, 1H), 7.88 (dd, J = 8.6, 6.3 Hz, 2H), 7.56 - 7.51 (m, 3H), 7.44 - 7.40 (m, 2H), 7.33 (dd, J = 9.4, 3.7 Hz, 3H), 7.23 (d, J = 2.5 Hz, 1H), 7.20 (d, J = 2.2 Hz, 1H), 3.93 (s, 3H).

[0147] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 164.1, 161.7, 159.1, 158.6, 137.0, 135.3, 132.9, 132.5, 132.3, 130.6, 130.3, 129.6, 129.4, 128.4, 128.2, 128.1, 128.0, 126.9, 126.6, 119.2, 105.5, 55.2.

[0148] MS (EI, 70 eV) m / z 420, 343, 300, 134, 77.

[0149] Example 13

[0150] The 4-([1,1'-biphenyl]-4-yl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0151]

[0152] 0.1 mmol of (E)-3-(dimethylamino)-1-([1,1'-biphenyl]-4-yl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added into a reaction tube, and stirred at 110 °C in an oil bath for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1, obtaining the purified target product 4-([1,1'-biphenyl]-4-yl)-2-phenyl-5-(phenylthio)pyrimidine compound with a yield of 81% and a purity of 99.9%;

[0153] The structure of the obtained product was characterized, and the structure characterization data was as follows:

[0154] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.66(dd, J = 7.6, 2.1 Hz, 2H), 8.62(s, 1H), 8.12(d, J = 8.4 Hz, 2H), 7.82(d, J = 8.4 Hz, 2H), 7.77 - 7.72(m, 2H), 7.61 - 7.51(m, 5H), 7.46(dd, J = 7.8, 1.6 Hz, 3H), 7.38(qd, J = 6.6, 5.8, 2.2 Hz, 3H).

[0155] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 163.8, 161.8, 159.2, 142.7, 140.2, 136.9, 136.2, 132.8, 132.2, 130.6, 129.8, 129.6, 128.7, 128.4, 128.2, 128.1, 127.9, 127.6, 127.1, 126.8.

[0156] MS(EI, 70 eV) m / z 416, 339, 312, 261, 234.

[0157] Example 14

[0158] The (E)-2-phenyl-5-(phenylthio)-4-styrylpyrimidine compound obtained in this example has the structure shown below:

[0159]

[0160] 0.1 mmol of (1E,4E)-1-(dimethylamino)-5-phenyl-1,4-dien-3-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1. The purified target product, (E)-2-phenyl-5-(phenylthio)-4-styrylpyrimidine compound, was obtained with a yield of 87% and a purity of 99.9%.

[0161] The structure of the obtained product was characterized, and the structure characterization data was as follows:

[0162] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.74 (s, 1H), 8.69 - 8.59 (m, 2H), 8.35 (d, J = 15.6 Hz, 1H), 7.76 - 7.64 (m, 3H), 7.58 (d, J = 5.7 Hz, 3H), 7.46 - 7.27 (m, 8H).

[0163] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 162.8, 162.1, 161.9, 138.7, 137.2, 135.8, 134.6, 130.8, 129.7, 129.44, 129.42, 128.7, 128.5, 128.3, 128.0, 127.2, 125.0, 122.5.

[0164] MS (EI, 70 eV) m / z 366, 289, 262, 134, 77.

[0165] Example 15

[0166] The 4-(benzo[d][1,3]dioxol-5-yl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0167]

[0168] 0.1 mmol of (E)-3-(dimethylamino)-1-(benzo[d][1,3]dioxol-5-yl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added into a reaction tube, and stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1, and the purified target product 4-(benzo[d][1,3]dioxol-5-yl)-2-phenyl-5-(phenylthio)pyrimidine compound was obtained with a yield of 80% and a purity of 99.9%;

[0169] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0170] 1 1H NMR (400 MHz, CDCl3, ppm) δ 8.51 (dd, J = 9.4, 5.7 Hz, 3H), 7.51 (t, J = 6.2 Hz, 5H), 7.37 (dd, J = 22.6, 6.5 Hz, 5H), 6.95 (d, J = 8.5 Hz, 1H), 6.04 (s, 2H).

[0171] 13 13C{ 1 1H}NMR (100 MHz, CDCl3, ppm) δ 163.4, 161.7, 159.3, 159.2, 149.2, 147.6, 137.0, 132.9, 132.3, 131.3, 130.6, 129.7, 128.5, 128.3, 128.0, 127.5, 124.2, 109.8, 109.7, 107.9, 101.4

[0172] MS (EI, 70 eV) m / z 384, 307, 277, 249, 134.

[0173] Example 16

[0174] The 4-(2-furyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0175]

[0176] Add 0.1 mmol of (E)-3-(dimethylamino)-1-(2-furyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1, to obtain the purified target product 4-(2-furyl)-2-phenyl-5-(phenylthio)pyrimidine compound, with a yield of 62% and a purity of 99.9%;

[0177] Characterize the structure of the obtained product, and the structure characterization data are as follows:

[0178] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.50(dd, J = 6.6, 3.2 Hz, 2H), 8.44(s, 1H), 7.73(d, J = 1.5 Hz, 1H), 7.62(d, J = 3.5 Hz, 1H), 7.51 - 7.45(m, 5H), 7.40 - 7.34(m, 3H), 6.62(dd, J = 3.5, 1.7 Hz, 1H).

[0179] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 161.6, 159.40, 159.37, 152.4, 151.0, 145.2, 136.9, 132.5, 132.0, 130.7, 129.8, 128.5, 128.4, 128.0, 124.7, 116.2, 112.2.

[0180] MS(EI, 70 eV) m / z 330, 301, 253, 171, 134.

[0181] Example 17

[0182] The 4-(3-thienyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0183]

[0184] 0.1 mmol of (E)-3-(dimethylamino)-1-(3-thienyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added into a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product 4-(3-thienyl)-2-phenyl-5-(phenylthio)pyrimidine compound was obtained with a yield of 86% and a purity of 99.9%.

[0185] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0186] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.62 - 8.56 (m, 3H), 8.44 - 8.38 (m, 1H), 8.06 (d, J = 4.9 Hz, 1H), 7.56 - 7.51 (m, 3H), 7.43 - 7.31 (m, 6H).

[0187] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 162.0, 160.6, 158.9, 139.0, 136.9, 133.0, 131.2, 130.7, 129.6, 129.5, 128.8, 128.4, 128.0, 127.9, 125.6, 125.1.

[0188] MS (EI, 70 eV) m / z 346, 313, 269, 171, 134.

[0189] Example 18

[0190] The 4-(4-pyridyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0191]

[0192] Add 0.1 mmol of (E)-3-(dimethylamino)-1-(4-pyridyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 5:1, to obtain the purified target product 4-(4-pyridyl)-2-phenyl-5-(phenylthio)pyrimidine compound, with a yield of 45% and a purity of 99.9%;

[0193] Characterize the structure of the obtained product, and the structure characterization data are as follows:

[0194] 1 H NMR(400MHz,CDCl3,ppm)δ8.76(d,J=5.9Hz,2H),8.58(s,1H),8.47(dd,J=6.7,3.0Hz,2H),7.76(d,J=6.0Hz,2H),7.51-7.45(m,3H),7.32(s,5H).

[0195] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ162.3,162.0,159.8,149.8,144.7,136.4,132.2,132.1,131.0,129.8,128.6,128.5,128.2,128.1,123.3

[0196] MS(EI,70eV)m / z 341,264,237,134,77.

[0197] Example 19

[0198] The 4-(2-pyrazinyl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0199]

[0200] 0.1 mmol of (E)-3-(dimethylamino)-1-(2-pyrazinyl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product, 4-(2-pyrazinyl)-2-phenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 36% and a purity of 99.9%.

[0201] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0202] 1 H NMR (400 MHz, CDCl3, ppm) δ 9.77 (s, 1H), 8.79 - 8.68 (m, 2H), 8.47 (dd, J = 6.5, 2.9 Hz, 2H), 8.34 (s, 1H), 7.59 (dd, J = 6.3, 2.9 Hz, 2H), 7.51 - 7.41 (m, 6H).

[0203] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 159.9, 157.3, 155.3, 150.9, 145.4, 144.7, 142.0, 136.5, 134.8, 132.0, 131.5, 130.7, 129.4, 128.6, 127.8.

[0204] MS (EI, 70 eV) m / z 342, 265, 238, 134, 77.

[0205] Example 20

[0206] The 4-isopropyl-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0207]

[0208] 0.1 mmol of (E)-3-(dimethylamino)-1-isopropylprop-2-en-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1, obtaining the purified target product 4-isopropyl-2-phenyl-5-(phenylthio)pyrimidine compound with a yield of 62% and a purity of 99.9%;

[0209] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0210] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.58 - 8.53 (m, 3H), 7.51 (dd, J = 5.2, 2.0 Hz, 3H), 7.36 - 7.27 (m, 5H), 3.64 (p, J = 6.7 Hz, 1H), 1.37 (d, J = 6.7 Hz, 6H).

[0211] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 175.0, 162.7, 159.7, 137.3, 134.1, 130.6, 130.5, 129.5, 128.4, 128.14, 127.4, 126.3, 32.6, 21.2.

[0212] MS (EI, 70 eV) m / z 306, 278, 229, 202, 134.

[0213] Example 21

[0214] The 4-((3r,5r,7r)-adamantan-1-yl)-2-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0215]

[0216] Add 0.1 mmol of (E)-3-(dimethylamino)-1-((3r,5r,7r)-adamantan-1-yl)-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 20:1, obtaining the purified target product 4-((3r,5r,7r)-adamantan-1-yl)-2-phenyl-5-(phenylthio)pyrimidine compound, with a yield of 29% and a purity of 99.9%;

[0217] Characterize the structure of the obtained product. The structure characterization data is as follows:

[0218] 1 H NMR(400MHz,CDCl3,ppm)δ8.53(dd,J=6.7,2.6Hz,2H),8.48(s,1H),7.54–7.49(m,3H),7.31(p,J=8.9,8.0Hz,5H),2.50-2.40(m,6H),2.20(s,3H),1.85(d,J=11.9Hz,6H).

[0219] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ174.5,162.5,161.1,137.4,135.9,134.1,130.6,130.4,129.5,128.4,128.1,127.22,127.17,42.2,39.3,36.6,28.7.

[0220] MS(EI,70eV)m / z 262,247,236,222,183.398,365,341,321,134.

[0221] Example 22

[0222] The 2-(4-bromophenyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0223]

[0224] 0.1 mmol of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, 0.3 mmol of 4-bromobenzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1. The purified target product, 2-(4-bromophenyl)-4-phenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 43% and a purity of 99.9%.

[0225] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0226] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.47 (s, 1H), 8.38 (d, J = 8.5 Hz, 2H), 7.96 - 7.88 (m, 2H), 7.61 (d, J = 8.5 Hz, 2H), 7.58 - 7.51 (m, 3H), 7.44 - 7.32 (m, 5H).

[0227] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 164.1, 160.8, 158.7, 137.2, 135.9, 132.7, 132.4, 131.6, 130.0, 129.7, 129.6, 129.2, 128.8, 128.5, 128.2, 125.4.

[0228] MS (EI, 70 eV) m / z 420, 343, 262, 165, 134.

[0229] Example 23

[0230] The 2-(4-methoxyphenyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0231]

[0232] 0.1 mmol of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, 0.3 mmol of 4-methoxybenzimidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added into a reaction tube, and stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1, and the purified target product 2-(4-methoxyphenyl)-4-phenyl-5-(phenylthio)pyrimidine compound was obtained, with a yield of 42% and a purity of 99.9%;

[0233] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0234] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.55 (s, 1H), 8.52 - 8.47 (m, 2H), 7.95 - 7.89 (m, 2H), 7.54 - 7.49 (m, 3H), 7.37 - 7.27 (m, 5H), 7.03 - 6.99 (m, 2H), 3.87 (s, 3H).

[0235] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 164.7, 161.92, 161.85, 159.8, 137.6, 133.6, 131.7, 129.83, 129.81, 129.6, 129.5, 129.3, 128.1, 127.9, 126.5, 113.8, 55.3.

[0236] MS (EI, 70 eV) m / z 370, 293, 250, 165, 134.

[0237] Example 24

[0238] The 2-(3-bromophenyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0239]

[0240] 0.1 mmol of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, 0.3 mmol of 3-bromobenzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product, 2-(3-bromophenyl)-4-phenyl-5-(phenylthio)pyrimidine compound, was obtained with a yield of 59% and a purity of 99.9%.

[0241] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0242] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.68 (t, J = 1.7 Hz, 1H), 8.51 - 8.40 (m, 2H), 7.92 (dd, J = 6.7, 3.0 Hz, 2H), 7.60 (ddd, J = 7.9, 1.9, 1.0 Hz, 1H), 7.58 - 7.52 (m, 3H), 7.43 - 7.32 (m, 6H).

[0243] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 164.0, 160.2, 158.5, 139.0, 137.1, 133.4, 132.8, 132.2, 131.0, 130.1, 130.0, 129.7, 129.2, 129.2, 128.6, 128.2, 126.5, 122.8.

[0244] MS (EI, 70 eV) m / z 420, 343, 262, 165, 134.

[0245] Example 25

[0246] The 2-(3-methoxyphenyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0247]

[0248] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of 3-methoxybenzimidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1, obtaining the purified target product 2-(3-methoxyphenyl)-4-phenyl-5-(phenylthio)pyrimidine compound with a yield of 79% and a purity of 99.9%;

[0249] Characterize the structure of the obtained product, and the structure characterization data are as follows:

[0250] 1 H NMR(400MHz,CDCl3,ppm)δ8.53(s,1H),8.19-8.14(m,1H),8.11(dd,J=2.4,1.5Hz,1H),7.95(dd,J=6.5,3.2Hz,2H),7.57-7.51(m,3H),7.45-7.31(m,6H),7.07(ddd,J=8.2,2.6,0.8Hz,1H),3.90(s,3H).

[0251] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ164.2,161.6,159.8,158.9,138.4,137.4,132.7,132.5,129.9,129.6,129.5,129.3,128.30,128.26,128.1,120.7,117.1,112.6,55.3.

[0252] MS(EI,70eV)m / z 370,293,250,165,134.

[0253] Example 26

[0254] The 2-(2-fluorophenyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0255]

[0256] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of 2-fluorobenzamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1, to obtain the purified target product 2-(2-fluorophenyl)-4-phenyl-5-(phenylthio)pyrimidine compound, with a yield of 77% and a purity of 99.9%;

[0257] Characterize the structure of the obtained product, and the structure characterization data are as follows:

[0258] 1 H NMR(400MHz,CDCl3,ppm)δ8.51(s,1H),8.19(td,J=7.8,1.8Hz,1H),7.98–7.91(m,2H),7.56-7.50(m,3H),7.47-7.33(m,6H),7.27-7.18(m,2H).

[0259] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ163.6,161.2(d,J=255.9Hz),160.1(d,J=5.0Hz),157.9,137.1,133.2,131.71,131.67,131.6,130.0,129.7,129.2,129.0,128.7,128.2,125.8(d,J=9.1Hz),124.0(d,J=3.8Hz),116.8(d,J=22.5Hz).

[0260] MS(EI,70eV)m / z 358,281,208,165,134.

[0261] Example 27

[0262] The 2-(2-methylphenyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0263]

[0264] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of 2-methylbenzimidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1, obtaining the purified target product 2-(2-methylphenyl)-4-phenyl-5-(phenylthio)pyrimidine compound with a yield of 77% and a purity of 99.9%;

[0265] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0266] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.56(s, 1H), 8.05 - 8.00(m, 1H), 7.98 - 7.90(m, 2H), 7.53(dd, J = 5.2, 1.8 Hz, 3H), 7.48 - 7.42(m, 2H), 7.36(p, J = 5.6 Hz, 6H), 2.70(s, 3H).

[0267] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 164.4, 163.6, 158.2, 137.5, 137.3, 137.2, 132.7, 132.3, 131.3, 130.5, 129.9, 129.7, 129.4, 129.2, 128.4, 128.1, 127.7, 125.8, 21.6.

[0268] MS(EI, 70 eV) m / z 354, 321, 275, 244, 116.

[0269] Example 28

[0270] The 2-(3-pyridyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0271]

[0272] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, 0.3 mmol of 3-pyridinecarboxamidine, 0.3 mmol of S-phenyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 20:1, obtaining the purified target product 2-(3-pyridyl)-4-phenyl-5-(phenylthio)pyrimidine compound with a yield of 43% and a purity of 99.9%;

[0273] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0274] 1 H NMR(400MHz,CDCl3,ppm)δ9.68(s,1H),8.70(t,J=6.8Hz,2H),8.45(s,1H),7.94–7.85(m,2H),7.56-7.49(m,3H),7.37(ddd,J=16.1,6.9,4.2Hz,6H).

[0275] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ163.9,159.7,158.4,151.2,149.7,137.0,135.2,133.0,132.5,132.0,130.1,129.8,129.6,129.2,128.7,128.2,123.2.

[0276] MS(EI,70eV)m / z 341,264,237,165,134.

[0277] Example 29 [[ID=2I]]

[0278] The 2-(4-pyridyl)-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0279]

[0280] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of 4-pyridinecarboxamidine, 0.3 mmol of S-phenyl benzenesulfonate, and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 5:1, obtaining the purified target product 2-(4-pyridyl)-4-phenyl-5-(phenylthio)pyrimidine compound with a yield of 53% and a purity of 99.9%.

[0281] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0282] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.73(d, J = 5.9 Hz, 2H), 8.39(s, 1H), 8.36 - 8.25(m, 2H), 7.89(dd, J = 6.5, 2.7 Hz, 2H), 7.51(d, J = 3.8 Hz, 3H), 7.46 - 7.30(m, 5H).

[0283] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 163.4, 159.1, 157.6, 150.2, 144.1, 136.8, 133.4, 131.2, 131.1, 130.1, 129.8, 129.1, 128.9, 128.2, 121.5.

[0284] MS(EI, 70 eV) m / z 341, 264, 237, 165, 134.

[0285] Example 30

[0286] The 4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0287]

[0288] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of formamidine, 0.3 mmol of S-phenyl benzenesulfonate, and 1 mL of dimethyl sulfoxide into a reaction tube. Stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1 to obtain the purified target product 4-phenyl-5-(phenylthio)pyrimidine compound with a yield of 92% and a purity of 99.9%;

[0289] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0290] 1 H NMR(400MHz,CDCl3,ppm)δ9.05(s,1H),8.36(s,1H),7.79(dd,J=6.6,3.0Hz,2H),7.52-7.47(m,3H),7.37(ddd,J=15.5,7.1,3.4Hz,5H).

[0291] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ163.7,157.6,155.6,136.9,133.2,131.6,130.1,129.8,129.0,128.8,128.3.

[0292] MS(EI,70eV)m / z 264,187,160,134,77.

[0293] Example 31

[0294] The 2-tert-butyl-4-phenyl-5-(phenylthio)pyrimidine compound obtained in this example has the following structure:

[0295]

[0296] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of tert-butylformamidine, 0.3 mmol of S-phenyl benzenesulfonate, and 1 mL of dimethyl sulfoxide into a reaction tube. Stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1 to obtain the purified target product 2-tert-butyl-4-phenyl-5-(phenylthio)pyrimidine compound with a yield of 37% and a purity of 99.9%;

[0297] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0298] 1 1H NMR (400 MHz, CDCl3, ppm) δ 8.41 (s, 1H), 7.87 (dd, J = 6.3, 2.6 Hz, 2H), 7.51 - 7.46 (m, 3H), 7.33 (dt, J = 13.2, 6.7 Hz, 5H), 1.46 (s, 9H).

[0299] 13 13C{ 1 1H}NMR (100 MHz, CDCl3, ppm) δ 174.8, 163.5, 158.6, 137.7, 132.9, 132.4, 129.8, 129.6, 129.4, 128.2, 128.1, 126.4, 39.1, 29.6.

[0300] MS (EI, 70 eV) m / z 320, 305, 278, 165, 134.

[0301] Example 3

[0302] The 4-phenyl-3-(phenylthio)benzo[4,5]imidazo[1,2-a]pyrimidine compound obtained in this example has the following structure:

[0303]

[0304] 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of 2-aminobenzimidazole, 0.3 mmol of S-phenyl benzenesulfonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 2:1. The purified target product, 4-phenyl-3-(phenylthio)benzo[4,5]imidazo[1,2-a]pyrimidine compound, was obtained with a yield of 40% and a purity of 99.9%;

[0305] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0306] 1H NMR (400MHz, CDCl3) δ8.81 (s, 1H), 7.94 (d, J = 8.2Hz, 1H, ppm), 7.65 (dt, J = 28.3, 7.3Hz ,3H),7.46-7.37(m,3H),7.26-7.09(m,5H),7.04-6.95(m,1H),6.21(d,J=8.5Hz,1H).

[0307] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ159.9,151.4,150.3,144.8,135.9,130.9,130.8, 129.5,129.2,128.9,128.1,127.6,126.9,126.2,122.0,120.4,114.6,113.2.

[0308] MS(EI,70eV)m / z 353,320,276,243,134.

[0309] Example 33

[0310] The 2,4-diphenyl-5-(p-tolylthio)pyrimidine compound obtained in this example has the following structure:

[0311]

[0312] 0.1 mmol (E)-3-(dimethylamino)-1-phenyl-2-propene-1-one, 0.3 mmol benzamidine, 0.3 mmol S-(p-tolyl)thiobenzenesulfonate and 1 mL dimethyl sulfoxide were added to a reaction tube and stirred in an oil bath at 110°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate in the eluent was 30:1. The purified target product 2,4-diphenyl-5-(p-tolylthio)pyrimidine compound was obtained with a yield of 80% and a purity of 99.9%.

[0313] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0314] 1 H NMR (400MHz, CDCl3, ppm) δ8.81-8.44(m,3H),8.02(s,2H),7.71-7.18(m,10H),2.42(d,J=6.7Hz,3H).

[0315] 13 C{ 11H NMR (100 MHz, CDCl3, ppm) δ 163.4, 161.4, 158.0, 158.0, 138.9, 137.5, 137.1, 130.5, 129.9, 129.3, 128.4, 128.1, 128.0, 21.1 21.1.

[0316] MS (EI, 70 eV) m / z 354, 263, 223, 147, 77.

[0317] Example 34

[0318] The 2,4-diphenyl-5-(4-chlorophenylthio)pyrimidine compound obtained in this example has the structure shown below:

[0319]

[0320] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-(4-chlorophenyl) benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1 to obtain the purified target product 2,4-diphenyl-5-(4-chlorophenylthio)pyrimidine compound with a yield of 83% and a purity of 99.9%;

[0321] Characterize the structure of the obtained product, and the structure characterization data are as follows:

[0322] 1 1H NMR (400 MHz, CDCl3, ppm) δ 8.75 - 8.53 (m, 3H), 8.06 - 7.92 (m, 2H), 7.68 - 7.51 (m, 6H), 7.36 (dt, J = 18.7, 9.1 Hz, 4H).

[0323] 13 13C{ 1 1H}NMR (100 MHz, CDCl3, ppm) δ 164.8, 162.2, 159.51, 159.48, 137.2, 136.8, 134.3, 133.2, 131.7, 130.8, 130.0, 129.7, 129.2, 128.5, 128.1, 127.2.

[0324] MS (EI, 70 eV) m / z 374, 263, 236, 165, 77.

[0325] Example 35

[0326] The 2,4-diphenyl-5-(2-fluorophenylthio)pyrimidine compound obtained in this example has the following structure:

[0327]

[0328] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-(2-fluorophenyl) benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1. The purified target product 2,4-diphenyl-5-(2-fluorophenylthio)pyrimidine compound is obtained, with a yield of 89% and a purity of 99.9%;

[0329] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0330] 1 H NMR(400MHz,CDCl3,ppm)δ8.55(dd,J=7.5,3.8Hz,3H),7.95(dd,J=6.4,2.8Hz,2H),7.57-7.49(m,6H),7.37-7.30(m,2H),7.11(q,J=7.3,6.5Hz,2H).

[0331] 13 C{ 1 H}NMR(100MHz,CDCl3,ppm)δ163.3(d,J=239.7Hz),161.8(d,J=248.8Hz),158.6(d,J=3.0Hz),137.4,136.9,134.7,130.9,130.8,130.7,130.0,129.2,128.5,128.2,128.1,126.6,125.1,119.6(d,J=17.9Hz),116.4(d,J=22.2Hz).

[0332] MS(EI,70eV)m / z 366,332,286,252,226.

[0333] Example 36

[0334] The 2,4-diphenyl-5-(2-pyridyl)pyrimidine compound obtained in this example has the following structure:

[0335]

[0336] 0.1 mmol of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-(2-pyridyl) benzenesulfonate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 10:1. The purified target product, 2,4-diphenyl-5-(2-pyridyl)pyrimidine compound, was obtained with a yield of 68% and a purity of 99.9%.

[0337] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0338] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.99 (d, J = 8.7 Hz, 1H), 8.68 - 8.57 (m, 2H), 8.42 - 8.29 (m, 1H), 7.96 - 7.84 (m, 2H), 7.49 (d, J = 26.5 Hz, 7H), 7.10 - 6.95 (m, 2H).

[0339] 13 C{ 1 H} NMR (100 MHz, CDCl3, ppm) δ 167.5164.04, 164.02, 163.5, 157.8, 149.8, 149.7, 137.4, 136.9, 136.7, 130.9, 129.7, 129.3, 128.41, 128.38, 127.8, 122.4, 122.2, 120.7.

[0340] MS (EI, 70 eV) m / z 341, 264, 210, 135, 77.

[0341] Example 37

[0342] The 2-((2,4-diphenylpyrimidin-5-yl)thio)benzothiazole compound obtained in this example has the following structure:

[0343]

[0344] 0.1 mmol of (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, 0.3 mmol of benzamidine, 0.3 mmol of S-(benzothiazol-2-yl) benzenecarbothioate and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1, to obtain the purified target product 2-((2,4-diphenylpyrimidin-5-yl)thio)benzothiazole compound with a yield of 63% and a purity of 99.9%;

[0345] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0346] 1 H NMR (400 MHz, CDCl3, ppm) δ 9.13 (s, 1H), 8.67 - 8.60 (m, 2H), 7.92 (dd, J = 6.5, 3.2 Hz, 2H), 7.87 (d, J = 8.2 Hz, 1H), 7.68 (d, J = 7.9 Hz, 1H), 7.54 (dd, J = 5.3, 1.9 Hz, 3H), 7.48 (dd, J = 5.0, 1.8 Hz, 3H), 7.44 - 7.39 (m, 1H), 7.31 - 7.27 (m, 1H).

[0347] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 168.2, 165.8, 164.8, 164.49, 164.47, 153.5, 136.9, 136.5, 135.5, 131.5, 130.3, 129.5, 128.8, 128.6, 128.2, 126.4, 124.7, 122.2, 121.4, 120.9.

[0348] MS (EI, 70 eV) m / z 396, 364, 320, 263, 167.

[0349] Example 38

[0350] The 2,4-diphenyl-5-(phenylseleno)pyrimidine compound obtained in this example has the following structure:

[0351]

[0352] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of Se-phenyl benzenesulfonate, and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1 to obtain the purified target product 2,4-diphenyl-5-(phenylseleno)pyrimidine compound with a yield of 68% and a purity of 99.9%;

[0353] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0354] 1 H NMR(400 MHz, CDCl3, ppm) δ 8.53(d, J = 5.2 Hz, 3H), 7.93 - 7.82(m, 2H), 7.61 - 7.47(m, 8H), 7.36(q, J = 7.0 Hz, 3H).

[0355] 13 C{ 1 H}NMR(100 MHz, CDCl3, ppm) δ 164.9, 162.1, 159.5 159.4, 138.5, 137.0, 135.1, 130.6, 130.0, 129.8, 128.8, 128.5, 128.3, 128.1, 128.0, 125.0.

[0356] MS(EI, 70 eV) m / z 343, 326, 313, 298, 271.

[0357] Example 39

[0358] The 2,4-diphenyl-5-(4-fluorophenylseleno)pyrimidine compound obtained in this example has the following structure:

[0359]

[0360] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of Se-(4-fluorophenyl) benzenesulfonate, and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1 to obtain the purified target product 2,4-diphenyl-5-(4-fluorophenylseleno)pyrimidine compound with a yield of 38% and a purity of 99.9%;

[0361] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0362] 1 H NMR (400 MHz, CDCl3 ppm) δ 8.57 - 8.41 (m, 3H), 7.88 - 7.78 (m, 2H), 7.58 - 7.46 (m, 8H), 7.04 (t, J = 8.4 Hz, 2H).

[0363] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 164.9, 163.4 (d, J = 250.1 Hz), 162.3, 159.1 (d, J = 3.3 Hz), 138.5, 137.7 (d, J = 8.3 Hz), 137.1, 130.8, 130.2, 128.9, 128.6, 128.5, 128.1, 125.2, 122.6 (d, J = 3.9 Hz), 117.3 (d, J = 21.7 Hz).

[0364] MS (EI, 70 eV) m / z 406, 311, 196, 12077.

[0365] Example 40

[0366] The 2,4-diphenyl-5-(3,4-dimethoxybenzeneselenyl)pyrimidine compound obtained in this example has the following structure:

[0367]

[0368] 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of Se-(3,4-dimethoxyphenyl)thiosulfonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube, and the mixture was stirred and reacted in an oil bath at 110 °C for 12 h. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 10:1. The purified target product, 2,4-diphenyl-5-(3,4-dimethoxybenzeneselenyl)pyrimidine compound, was obtained with a yield of 35% and a purity of 99.9%;

[0369] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0370] 11H NMR (400 MHz, CDCl3, ppm) δ 8.50 - 8.45 (m, 2H), 8.38 (s, 1H), 7.88 - 7.83 (m, 2H), 7.55 (dd, J = 5.1, 1.9 Hz, 3H), 7.48 - 7.44 (m, 3H), 7.21 (dd, J = 8.2, 1.9 Hz, 1H), 7.07 (d, J = 1.8 Hz, 1H), 6.85 (d, J = 8.3 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H).

[0371] 13 C{ 1 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 163.9, 161.7, 158.0, 150.2, 149.7, 138.5, 137.1, 130.5, 130.0, 129.5, 128.7, 128.42, 128.37, 127.8, 126.1, 118.8, 117.1, 112.2, 56.0, 55.9.

[0372] MS (EI, 70 eV) m / z 448, 367, 311, 281, 77.

[0373] Example 41

[0374] The 2,4 - diphenyl - 5 - (methylseleno)pyrimidine compound obtained in this example has the following structure:

[0375]

[0376] Add 0.1 mmol of (E)-3-(dimethylamino)-1-phenyl-2-propen-1-one, 0.3 mmol of benzamidine, 0.3 mmol of Se-methyl benzenesulfonate and 1 mL of dimethyl sulfoxide into a reaction tube, stir and react in an oil bath at 110 °C for 12 h. After the reaction is completed, separate and purify by column chromatography. The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent is 30:1. The purified target product, 2,4 - diphenyl - 5 - (methylseleno)pyrimidine compound, is obtained with a yield of 23% and a purity of 99.9%;

[0377] Characterize the structure of the obtained product. The structure characterization data are as follows:

[0378] 11H NMR (400 MHz, CDCl3, ppm) δ 8.79 (s, 1H), 8.51 (dd, J = 6.7, 3.0 Hz, 2H), 7.83 (dd, J = 6.6, 2.9 Hz, 2H), 7.55 - 7.47 (m, 6H), 2.32 (s, 3H).

[0379] 13 13C{ 1 1H} NMR (100 MHz, CDCl3, ppm) δ 165.3, 161.8, 157.6, 138.6, 137.2, 130.5, 130.0, 128.8, 128.5, 128.3, 128.0, 123.9, 7.6.

[0380] MS (EI, 70 eV) m / z 326, 311, 284, 181, 77.

[0381] Application Example 1

[0382] 2,4-Diphenyl-5-(phenylthio)pyrimidine prepared in Example 1 was used to prepare 2,4-diphenyl-5-(phenylsulfinyl)pyrimidine compound. The structural formula of the product is as follows:

[0383]

[0384] 0.1 mmol of 2,4-diphenyl-5-(phenylthio)pyrimidine, 0.2 mmol of potassium peroxymonosulfate and 1.5 mL of dichloromethane were added to a reaction tube. The mixture was stirred at room temperature for 24 hours. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 5:1. The purified target product was 2,4-diphenyl-5-(phenylsulfinyl)pyrimidine compound, with a yield of 83% and a purity of 99.9%;

[0385] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0386] 1 1H NMR (400 MHz, CDCl3, ppm) δ 9.36 (s, 1H), 8.55 (dd, J = 7.6, 1.9 Hz, 2H), 7.75 - 7.66 (m, 2H), 7.57 - 7.43 (m, 6H), 7.34 - 7.18 (m, 5H).

[0387] 13 13C{ 11H NMR (100 MHz, CDCl3, ppm) δ 165.5, 164.0, 155.1, 143.3, 136.2, 136.1, 135.3, 131.5, 131.3, 130.6, 129.2, 129.0, 128.62, 128.60, 128.4, 124.9.

[0388] MS (EI, 70 eV) m / z 356, 218, 141, 125, 77.

[0389] Application Example 2

[0390] 4-(4-Iodophenyl)-2-phenyl-5-(phenylthio)pyrimidine prepared in Example 3 was used to prepare 2-phenyl-4-(4-(phenylethynyl)phenyl)-5-(phenylthio)pyrimidine compound, and the structural formula of the product is as follows:

[0391]

[0392] 0.1 mmol of 4-(4-iodophenyl)-2-phenyl-5-(phenylthio)pyrimidine, 0.12 mmol of benzyne, 0.01 mol of copper(I) iodide, 0.005 mmol of bis(triphenylphosphine)palladium(II) dichloride, 0.5 mL of triethylamine and 1 mL of tetrahydrofuran were added to a reaction tube. Under a N2 atmosphere, the mixture was refluxed in an oil bath at 50 °C for 24 hours. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 20:1. The purified target product was 2-phenyl-4-(4-(phenylethynyl)phenyl)-5-(phenylthio)pyrimidine compound, with a yield of 86% and a purity of 99.9%;

[0393] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0394] 1 1H NMR (400 MHz, CDCl3, ppm) δ 8.60 (d, J = 9.0 Hz, 3H), 8.06 - 7.96 (m, 2H), 7.78 - 7.39 (m, 15H).

[0395] 13 13C{ 1 1H}NMR (100 MHz, CDCl3, ppm) δ 163.5, 161.9, 159.4, 137.0, 136.9, 132.7, 132.3, 131.6, 131.3, 130.8, 129.7, 129.4, 128.51, 128.46, 128.3, 128.1, 128.0, 125.0, 122.9, 91.1, 89.0.

[0396] Application Example 3

[0397] 4-(4-Iodophenyl)-2-phenyl-5-(phenylthio)pyrimidine prepared in Example 3 was used to prepare (8R,9S,10R,13S,14S,17S)-17-hydroxy-13-methyl-17-((4-(2-phenyl-5-(phenylthio)pyrimidin-4-yl)phenyl)ethynyl)-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one compound, and the structural formula of the product is as follows:

[0398]

[0399] 0.1 mmol of 4-(4-iodophenyl)-2-phenyl-5-(phenylthio)pyrimidine, 0.12 mmol of norethindrone, 0.01 mmol of copper(I) iodide, 0.005 mmol of bis(triphenylphosphine)palladium(II) dichloride, 0.5 mL of triethylamine and 1 mL of tetrahydrofuran were added to a reaction tube. Under a nitrogen atmosphere, the mixture was refluxed in an oil bath at 50 °C for 24 hours. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 3:1. The purified target product was (8R,9S,10R,13S,14S,17S)-17-hydroxy-13-methyl-17-((4-(2-phenyl-5-(phenylthio)pyrimidin-4-yl)phenyl)ethynyl)-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one compound, with a yield of 90% and a purity of 99.9%;

[0400] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0401] 11H NMR (400 MHz, CDCl3, ppm) δ 8.51 - 8.44 (m, 3H), 7.87 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.3 Hz, 2H), 7.48 - 7.44 (m, 3H), 7.36 - 7.29 (m, 5H), 5.83 (s, 1H), 2.68 (s, 1H), 2.42 (d, J = 14.8 Hz, 2H), 2.28 - 2.23 (m, 2H), 2.09 (ddd, J = 20.7, 13.3, 6.1 Hz, 3H), 1.82 (ddd, J = 39.3, 21.9, 8.2 Hz, 5H), 1.58 (dt, J = 12.0, 6.3 Hz, 2H), 1.42 - 1.24 (m, 5H), 1.12 - 1.06 (m, 1H), 0.96 (s, 3H).

[0402] 13 C{ 1 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 199.9, 166.6, 163.4, 161.8, 159.3, 137.0, 136.7, 132.5, 132.2, 131.3, 130.7, 129.7, 129.2, 128.5, 128.3, 128.0, 127.9, 124.6, 124.4, 94.5, 85.5, 79.9, 49.4, 49.1, 47.4, 42.4, 40.9, 38.8, 36.4, 35.4, 32.7, 30.6, 26.4, 26.2, 22.9, 12.8.

[0403] Application Example 4

[0404] 4-(4-Iodophenyl)-2-phenyl-5-(phenylthio)pyrimidine prepared in Example 3 was used to prepare 3-(4-(2-phenyl-5-(phenylthio)pyrimidin-4-yl)phenyl)prop-2-yn-1-yl (R)-2-(4-((5-chloro-3-fluoropyridin-2-yl)oxy)phenoxy)propionate. The structural formula of the product is as follows:

[0405]

[0406] 0.1 mmol of 4-(4-iodophenyl)-2-phenyl-5-(phenylthio)pyrimidine, 0.12 mmol of clodinafop-propargyl, 0.01 mmol of cuprous iodide, 0.005 mmol of bis(triphenylphosphine)palladium dichloride, 0.5 mL of triethylamine and 1 mL of tetrahydrofuran were added to a reaction tube. Under a N2 atmosphere, the mixture was refluxed in an oil bath at 50 °C for 24 hours. After the reaction was completed, it was separated and purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 3:1. The purified target product was 3-(4-(2-phenyl-5-(phenylthio)pyrimidin-4-yl)phenyl)prop-2-yn-1-yl (R)-2-(4-((5-chloro-3-fluoropyridin-2-yl)oxy)phenoxy)propionate compound, with a yield of 56% and a purity of 99.9%;

[0407] The structure of the obtained product was characterized, and the structure characterization data was as follows:

[0408] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.55 - 8.46 (m, 3H), 7.92 - 7.84 (m, 3H), 7.57 (d, J = 8.2 Hz, 2H), 7.51 - 7.43 (m, 4H), 7.33 (dd, J = 6.0, 3.5 Hz, 5H), 7.09 (d, J = 9.0 Hz, 2H), 6.96 (d, J = 9.0 Hz, 2H), 5.04 (d, J = 1.8 Hz, 2H), 4.83 (q, J = 6.7 Hz, 1H), 1.70 (d, J = 6.8 Hz, 3H).

[0409] 13 C{ 1 H}NMR (100 MHz, CDCl3, ppm) δ 199.9, 166.6, 163.4, 161.8, 159.3, 137.0, 136.7, 132.5, 132.2, 131.3, 130.7, 129.7, 129.2, 128.5, 128.3, 128.0, 127.9, 124.6, 124.4, 94.5, 85.5, 79.9, 49.4, 49.1, 47.4, 42.4, 40.9, 38.8, 36.4, 35.4, 32.7, 30.6, 26.4, 26.2, 22.9, 12.8.

[0410] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing a selenium- or sulfur-containing pyrimidine heterocyclic compound, characterized in that, The steps are as follows: Mix an amidine compound or 2-aminobenzimidazole with an enaminone compound, a compound having the structural formula shown in Formula IV, and a polar organic solvent, and heat them to carry out an olefin addition reaction and a cyclization reaction. Then, purify the obtained product to obtain a selenium- or sulfur-containing pyrimidine heterocyclic compound; The selenium- or sulfur-containing pyrimidine heterocyclic compound has the structural formula shown in Formula I; The enaminone compound has the structure shown in Formula II: The amidine compound has the structure shown in Formula III: R 1 is a first aryl group, a first substituted aryl group, a first heteroaryl group or a first alkyl group; R 2 is a second aryl group, a second substituted aryl group, a second heteroaryl group, a second alkyl group or hydrogen; R 3 is a third aryl group, a third substituted aryl group, a third heteroaryl group or a third alkyl group; X is S or Se.

2. The preparation method according to claim 1, characterized in that, The first substituted aryl includes a halophenyl, a trifluoromethylphenyl, an alkylphenyl, an alkoxyphenyl, a nitrophenyl, a cyanophenyl, a vinylphenyl, or a methylenedioxyphenyl; The first aryl includes a phenyl, a naphthyl, or a biphenyl; The first heteroaryl includes a furyl, a thienyl, a pyridyl, or a pyrazinyl; The first alkyl includes an isopropyl or an adamantyl.

3. The preparation method according to claim 1, characterized in that, The second aryl includes a phenyl; The second substituted aryl includes a halophenyl, an alkylphenyl, or an alkoxyphenyl; The second heteroaryl includes a pyridyl or a pyrazinyl; The second alkyl includes a tert-butyl.

4. The preparation method according to claim 1, wherein The third aryl includes a phenyl; The third substituted aryl includes a halophenyl, an alkylphenyl, an alkoxyphenyl, or a benzothiazolyl; The third heteroaryl includes a pyridyl; The third alkyl includes a methyl.

5. The preparation method according to claim 1, wherein The selenium- or sulfur-containing pyrimidine heterocyclic compound has the structural formula shown in any one of Formula I-1 to Formula I-41:

6. The preparation method according to claim 1, characterized in that, The molar ratio of the enaminone compound to the amidine compound or 2-aminobenzimidazole is 1:1 to 3.

7. The preparation method according to claim 1, wherein The molar ratio of the enaminone compound to the compound having the structural formula shown in Formula IV is 1:1 to 3.

8. The preparation method according to claim 1, wherein The heating temperature is 60 to 120 °C, and the time is 3 to 24 h.

9. The preparation method according to claim 1, characterized in that, The polar organic solvent includes one or more of dimethyl sulfoxide, N,N-dimethylformamide, 1,2-dichloroethane, toluene, acetonitrile, N-methylpyrrolidone, and N,N-dimethylacetamide.

10. The preparation method according to claim 1 or 9, characterized in that, The dosage ratio of the polar organic solvent to the enaminone compound is 1 L: 0.1 to 1 mol.

Images