CN111925310A - 3-amino-4-arylseleno maleimide compound and preparation method thereof - Google Patents

Abstract

The invention relates to a 3-amido-4-arylseleno maleimide compound and a preparation method thereof, in an organic solvent and under the condition of oxygen, aromatic iodide, selenium powder, maleimide and secondary amine are taken as reaction raw materials, and the carbon-carbon double bond of the maleimide is simultaneously subjected to oxidative coupling reaction through relay reaction catalyzed by transition metal copper to obtain the 3-amido-4-arylseleno maleimide compound. The method has simple reaction conditions and high yield and purity of the product, develops a new synthetic route and method for preparing the 3-amido-4-arylseleno maleimide compound, and has good application potential and research value.

Description

A kind of 3-amino-4-arylselenyl maleimide compound and preparation method

technical field

The invention belongs to the technical field of organic compound synthesis, in particular to a 3-amino-4-arylselenyl maleimide compound and a preparation method.

Background technique

As an important class of amide compounds, maleimide widely exists in natural products, bioactive molecules and clinical drug molecules, and the parent structure can also be prepared by various conversion reactions to succinimide, pyrrolidine, lactam Therefore, based on the application of maleimide compounds in different fields, how to efficiently and greenly synthesize derivatives with maleimide skeleton has always been the goal pursued by organic chemists. For example: Professor Jiang Xianxing of Sun Yat-Sen University used organic base catalysts, 1,4-dithio-2,5-diol and maleimide as substrates to connect Michael-Aldol[3+2] rings through diastereoselective Diastereoselective Synthesis of Biheterocyclic TetrahydrothiopheneDerivatives via Base-Catalyzed Cascade Michael-Aldol[3+2]Annulation of 1,4-Dithiane-2,5-diol with Maleimides, J.Org.Chem., 2015, 80, 6870-6874), through pharmacological activity studies, it was found that such compounds have good biological and pharmaceutical activities at the same time; In 2008, A.Yu.Simonov et al. reported (Synthesis of 4-substituted 3-[3-(dialkylaminomethyl)indol-1-yl]maleimides and study of their ability to inhibit protein kinase Cα, prevent development of multiple drug resistance of tumor cells and cytotoxicity, Russ.Chem.Bull.2008,57,2011- 2020;), the use of 3-amino-4-arylmercaptomaleimide can inhibit protein kinases and prevent the development of multiple drug resistance and cytotoxicity of tumor cells.

It is precisely because the compounds containing maleimide structures are so important that a lot of research has been carried out on their synthesis, especially the synthesis of 3-amino-4-arylmercaptomaleimide compounds. Synthetic route and method:

In 2002, Dubinina, G.G. et al. reported (Reactions of 3,4-dichloromaleimides with N-and S-nucleophiles, Ukrainskii Khimicheskii Zhurnal, 68, 47-51; 2002), using 3,4-dichloromaleimides with N-and S-nucleophiles , arylamine and thiophenol reflux under triethylamine condition to obtain 3-amino-4-arylmercaptomaleimide compound, but this reaction needs expensive 3,4-dichloromaleimide as raw material, Even the use of foul-smelling thiophenols is likely to cause environmental pollution. The reaction formula is as follows:

In 2018, Professor Zhao Shengyin of Donghua University and others reported (Three-Component CouplingReactions of Maleimides, Thiols, and Amines: One-Step Construction of 3,4-Heteroatom-functionalized Maleimides by Copper-Catalyzed C(sp2)-HThioamination, Advanced Synthesis & Catalysis, 2018, 360, 173-179;), 3-amino-4-arylmercaptomaleimide via the three-component tandem reaction of maleimide, arylamine and thiophenol catalyzed by transition metal copper/oxygen The preparation of the amine target compound, the use of malodorous thiophenols is easy to cause environmental pollution, and the reaction formula is as follows:

In recent years, seleno-substituted maleimides have also been reported. In 2017, Mahiuddin Baidya et al. from the Indian Institute of Technology reported (Ru(II)-Catalyzed C-H Functionalization on Maleimides with Electrophiles: A Demonstration of Umpolung Strategy, Org. Lett., 2017,19,1902-1905;), utilize expensive ruthenium catalyzed maleimide and diaryl diselenide to synthesize 3-arylselenyl maleimide, the reaction formula is as follows:

Although the existing technology can solve the arylselenylation reaction of maleimide, the use of pre-prepared diaryl diselenyl ethers and expensive ruthenium catalysts in the reaction process limits the further industrial application of this reaction and the utilization of molecular compounds. Pharmacological activity or biological activity research, and the synthesis of a series of 3-amino-4-arylselenomaleimide compounds through bifunctionalization of carbon-carbon double bonds in the maleimide structure has not been reported so far. Therefore, it is particularly important to prepare 3-amino-4-arylselenylmaleimide compounds from raw materials that are simple, easy to handle, and cheap and easy to obtain substrates, especially the use of elemental selenium as a selenoylation reagent The 3-amino-4-arylselenyl maleimide compound is synthesized by the series reaction of the components, and there is still a need for continued research and exploration, which is also the basis and motivation for the completion of the present invention.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is the synthetic route problem of the preparation method of the 3-amino-4-arylselenylmaleimide compound.

For solving the above technical problems, the present invention provides the following technical solutions:

A kind of preparation method of 3-amino-4-arylselenyl maleimide compound, in organic solvent, under oxygen condition, with the aromatic iodide having the structure shown in formula (I), formula (II) The selenium powder of the shown structure, the maleimide compound of the structure shown in (III) and the secondary amine shown in the structure of formula (IV) are the reaction raw materials, and under the catalysis of transition metal copper, the maleimide compound is passed through the maleimide. The oxidative coupling reaction of the carbon-carbon double bond in the structure obtains the 3-amino-4-arylselenylmaleimide compound of the structure represented by formula (V).

The above-mentioned reaction process can be represented by the following reaction formula:

The aromatic iodide of the structure shown in (I), the selenium powder of the structure of the formula (II), the maleimide of the structure of the formula (III) and the secondary amine of the structure of the formula (IV) The molar ratio was 6:6:2:3.

(1) Aromatic iodide

Aromatic iodides in the present invention include iodobenzene, 1-iodonaphthalene, 4-methyliodobenzene, 4-fluoroiodobenzene, 4-chloroiodobenzene, 4-bromoiodobenzene, 4-nitroiodobenzene, 4- Trifluoromethyliodobenzene, 4-cyanoiodobenzene and 3-iodothiophene.

(2) Maleimide compound

Maleimide compounds in the present invention include maleimide, N-phenylmaleimide, N-benzylmaleimide, N-cyclohexylmaleimide and N-( 2-Thienylmethyl)maleimide

(3) Secondary amine

Secondary amines in the present invention include morpholine, thiomorpholine, tetrahydropyrrole, cyclohexylimine, 4-piperidinemethanol and methyl 4-piperidinecarboxylate.

(4) transition metal catalyst copper

The transition metal catalyst copper in the present invention is copper acetate, copper chloride, copper bromide or cuprous iodide, preferably copper acetate, and in molar terms, the ratio of the consumption of the copper acetate to the consumption of the formula (II) It is 0.1:1-0.3:1, preferably 0.1.

(5) Organic solvent

The reaction solvent in the present invention is an organic solvent, and the organic solvent is dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dichloromethane , at least one of ethyl acetate, pyridine, 1,4-dioxane, 1,2-dichloroethane, acetonitrile, toluene, tetrahydrofuran, ethanol, carbon tetrachloride, chloroform, n-butanol, preferably N-methylpyrrolidone.

(6) Alkali

The base in the present invention is an inorganic base, and the base is lithium carbonate, cesium carbonate, potassium carbonate, sodium carbonate, sodium acetate, lithium acetate, potassium phosphate, sodium tert-butoxide, lithium tert-butoxide or potassium tert-butoxide, preferably for sodium carbonate.

(7) Reaction temperature

In the preparation method of the present invention, the reaction temperature is 100-120°C, for example, 100°C, 110°C and 120°C without limitation, and the reaction temperature is preferably 120°C.

(8) Response time

In the preparation method of the present invention, the reaction time is not particularly limited. For example, a suitable reaction time can be determined by detecting the residual percentage of the target product or raw material by liquid chromatography, which is usually 14-18 hours. The reaction time is preferably 18 hours, 14 hours, 15 hours, 16 hours, 17 hours or 18 hours.

(9) Separation and purification

The mixture obtained after the reaction can be further separated and purified to obtain a relatively pure final product. Those of ordinary skill in the art are familiar with separation and purification methods, for example, extraction, column chromatography, distillation, filtration, centrifugation, washing, fractionation and adsorption, or a combination of at least two, can be used for separation and purification, such as extraction and column chromatography.

Of course, if necessary, the obtained reaction mixture can also be directly introduced into other processes for direct reaction to produce other products. Optionally, the reaction mixture can be pre-treated, for example, by one or more experimental operations of concentration, extraction and distillation under reduced pressure, to obtain a crude or pure product, which is then introduced into the other processes.

In a preferred embodiment, the post-processing step after the reaction is completed can be the following method: after the reaction is completed, the reaction solution is cooled and then diluted with ethyl acetate, the diluted solution is transferred to a separatory funnel, saturated with Extract with brine, separate the aqueous phase and the organic phase, and then extract the aqueous phase with ethyl acetate three times, combine the organic phases, add 5 g of anhydrous sodium sulfate, stand for 30 min, and wash the filter cake with 5 mL of ethyl acetate each time for a total of 3 times. Then spin off the solvent, separate the concentrate by column chromatography (silica gel is 300-400 mesh silica gel), use petroleum ether and ethyl acetate mixture as eluent, collect the eluate, and concentrate to obtain the target product.

The preparation method of 3-amino-4-arylselenyl maleimide provided by the invention has the following beneficial effects:

a) high reaction efficiency, high yield and easy post-processing;

b) using elemental selenium as a selenoylation reagent to participate in the tandem reaction of four components;

c) Utilize cheap and easy copper/oxygen as catalytic system;

The present invention is represented by an aromatic iodide having a structure represented by formula (I), a selenium powder having a structure represented by formula (II), a maleimide having a structure represented by formula (III) and a structure represented by formula (IV) The secondary amine is the reaction raw material, under the catalysis of transition metal copper/oxygen, through the oxidative coupling reaction of the carbon-carbon double bond in the maleimide structure to obtain the 3-amino- 4-Arylselenomaleimide compound. This synthetic method will be an important development and supplement for the facile and low-cost synthetic method of 3-amino-4-arylselenylmaleimide, and provide a new strategy for the molecular design and synthesis of maleimide derivatives , has important social and economic significance.

Detailed ways

The present invention will be described in detail below through specific examples, but the purposes and purposes of these exemplary embodiments are only used to illustrate the present invention, and do not constitute any limitation to the actual protection scope of the present invention, nor do they limit the present invention. The scope of protection is limited to this.

The data and purity of the novel compounds given in the following examples were identified by nuclear magnetic resonance.

Example 1

Synthesis of 1-Methyl-3-morpholinyl-4-(1-naphthylselenyl)maleimide

At room temperature, 1-iodonaphthalene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv) , copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred for 18 h at the reaction temperature of 120 °C . The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 88%, and the weight of the product was 70 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 8.10 (d, J=8.2 Hz, 1H), 7.82 (d, J=7.9 Hz, 1H), 7.70 (d, J=7.7 Hz, 1H), 7.56- 7.49(m, 2H), 7.37-7.32(m, 2H), 4.13(t, J=4.70Hz, 4H), 3.58(t, J=4.70Hz, 4H), 3.06(s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125MHz, CDCl ₃ ): δ 170.3, 166.6, 150.5, 134.1, 132.3, 131.3, 128.7, 127.4, 127.3, 126.6, 126.4, 126.1, 125.5, 85.8, 67.0, 48.5, 24.5;

HRMS (ESI): _calcd for _C19H18N2O3Se [ _M +H] ⁺ _403.0562 , found 403.0566.

Example 2

Synthesis of 1-Methyl-3-morpholinyl-4-(4-methylphenylselenoyl)maleimide

At room temperature, 4-methyliodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5 equiv), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, at a reaction temperature of 120 °C Stir for 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 95%, and the weight of the product was 69 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.22 (d, J=8.0 Hz, 2H), 7.06 (d, J=8.0 Hz, 2H), 4.15 (t, J=4.70 Hz, 4H), 3.67 ( t, J=4.70Hz, 4H), 3.03 (s, 3H), 2.29 (s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125MHz, CDCl ₃ ): δ 170.5, 166.8, 149.6, 136.7, 135.9, 130.3, 130.2, 129.9, 128.5, 87.8, 66.9, 48.5, 24.4, 20.9;

HRMS (ESI): _calcd for _C16H18N2O3Se [ _M +H] ⁺ _367.0562 , found 367.0568.

Example 3

Synthesis of 1-Methyl-3-morpholinyl-4-(4-fluorophenylselenoyl)maleimide

At room temperature, 4-fluoroiodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv) were mixed together ), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at a reaction temperature of 120 °C 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 71%, and the weight of the product was 52 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.34-7.31 (m, 2H), 6.97 (t, J=8.7 Hz, 2H), 4.17 (t, J=4.70 Hz, 4H), 3.70 (t, J =4.70Hz, 4H), 3.03 (s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.3, 166.6, 162.1 (d, J _F =246.5 Hz), 149.7, 131.8 (d, J _F =7.7 Hz), 126.6 (d, J _F =3.4 Hz) , 116.6 (d, J _F =21.8Hz), 87.4, 66.9, 48.6, 4.4;

The data of the fluorine nuclear magnetic resonance spectrum of the obtained product are as follows:

¹⁹ F NMR (470 MHz, CDCl ₃ ): δ-115.1 (s, 1F);

HRMS (ESI): _calcd for _{C15H15FN2O3Se} [ _M +H] ⁺ _371.0311 , found 371.0317.

Example 4

Synthesis of 1-Methyl-3-morpholinyl-4-(4-chlorophenylselenoyl)maleimide

At room temperature, 4-chloroiodobenzene (0.6 mmol, 3 equiv), selenium powder (0.6 mmol, 3 equiv), N-methylmaleimide (0.2 mmol, 1 equiv), morpholine (0.3 mmol, 1.5 equiv) were mixed together ), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at a reaction temperature of 120 °C 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 74%, and the weight of the product was 57 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.23 (dd, J=16.5, 8.7 Hz, 4H), 4.17 (t, J=4.70 Hz, 4H), 3.70 (t, J=4.70 Hz, 4H), 3.04(s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.2, 166.5, 150.0, 132.8, 130.7, 130.6, 129.6, 86.4, 66.9, 48.6, 24.5;

HRMS (ESI): _calcd for _{C15H15ClN2O3Se} [ _M +H] ⁺ _387.0015 , found 387.0022.

Example 5

Synthesis of 1-Methyl-3-morpholinyl-4-(4-bromophenylselenoyl)maleimide

At room temperature, 4-bromoiodobenzene (0.6 mmol, 3 equiv), selenium powder (0.6 mmol, 3 equiv), N-methylmaleimide (0.2 mmol, 1 equiv), morpholine (0.3 mmol, 1.5 equiv) were combined ), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at a reaction temperature of 120 °C 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 55%, and the weight of the product was 47 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.36 (d, J=8.3 Hz, 2H), 7.18 (d, J=8.4 Hz, 2H), 4.17 (t, J=4.70 Hz, 4H), 3.70 ( t, J=4.70Hz, 4H), 3.04(s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.2, 166.5, 150.1, 132.5, 131.4, 130.9, 120.7, 86.3, 66.9, 48.6, 24.5;

HRMS (ESI): _calcd for _{C15H16BrN2O3Se} [ _M +H] ⁺ _430.9510 , found 430.9509.

Example 6

Synthesis of 1-Methyl-3-morpholinyl-4-(4-nitrophenylselenoyl)maleimide

At room temperature, 4-nitroiodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5 equiv), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, at a reaction temperature of 120 °C Stir for 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 47%, and the weight of the product was 37 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 8.09 (d, J=8.7 Hz, 2H), 7.40 (d, J=8.7 Hz, 2H), 4.19 (t, J=4.70 Hz, 4H), 3.73 ( t, J=4.70Hz, 4H), 3.10(s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 169.8, 166.1, 150.9, 146.4, 143.1, 128.4, 124.3, 83.9, 66.9, 48.7, 24.6;

HRMS (ESI): calcd for _C15H15N3O5Se [ _M +H] ⁺ _398.0256 , found _398.0259 .

Example 7

Synthesis of 1-Methyl-3-morpholinyl-4-(4-trifluoromethylphenylselenoyl)maleimide

At room temperature, 4-trifluoromethyl iodobenzene (0.6 mmol, 3 equiv), selenium powder (0.6 mmol, 3 equiv), N-methylmaleimide (0.2 mmol, 1 equiv), morpholine (0.3 mmol, 1 equiv) were mixed together , 1.5 equiv), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and reacted at 120 °C Stir at temperature for 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: diethyl ether=8 : 1), the product was a yellow liquid, the yield was 38%, and the weight of the product was 32 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.48 (d, J=8.1 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 4.18 (t, J=4.70 Hz, 4H), 3.71 ( t, J=4.70Hz, 4H), 3.06 (s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.0, 166.3, 150.6, 137.9, 128.7 (q, J _F =32.9 Hz), 128.7, 126.1 (q, J _F =3.9 Hz), 124.0 (q, J _F = 32.9 Hz) = 270.4Hz), 85.0, 66.9, 48.6, 24.5;

The data of the fluorine nuclear magnetic resonance spectrum of the obtained product are as follows:

¹⁹ F NMR (470 MHz, CDCl ₃ ): δ-62.6 (s, 3F);

HRMS (ESI): _calcd for _{C16H15F3N2O3Se [ M} +H] ⁺ _421.0279 , found 421.0280.

Example 8

Synthesis of 1-Methyl-3-morpholinyl-4-(4-cyanophenylselenyl)maleimide

At room temperature, 4-cyanoiodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5 equiv), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, at a reaction temperature of 120 °C Stir for 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 51%, and the weight of the product was 38 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.52 (d, J=8.3 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 4.19 (t, J=4.70 Hz, 4H), 3.74 ( t, J=4.70Hz, 4H), 3.08 (s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 169.9, 166.2, 150.9, 140.4, 132.7, 128.7, 118.6, 109.9, 84.2, 66.9, 48.7, 24.6;

HRMS (ESI): calcd for _{C16H15N3O3Se [ M} +H] ⁺ _378.0358 , found 378.0360.

Example 9

Synthesis of 1-Methyl-3-morpholinyl-4-(3-thienyl)maleimide

At room temperature, 3-iodothiophene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv) , copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred for 18 h at the reaction temperature of 120 °C . The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 82%, and the weight of the product was 59 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.32-7.31 (m, 1H), 7.21 (d, J=1.9 Hz, 1H), 7.05-7.04 (m, 1H), 4.19 (t, J=4.70 Hz) , 4H), 3.72 (t, J=4.70Hz, 4H), 3.03 (s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.4, 166.7, 149.1, 130.2, 126.7, 124.8, 124.5, 88.1, 66.9, 48.6, 24.4;

HRMS (ESI): _calcd for _{C13H14N2O3SSe} [ _M +H] ⁺ _358.9969 , found 358.9970.

Example 10

Synthesis of 3-Mormorpholinyl-4-Phenylselenomaleimide Compounds

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), maleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv), copper acetate (0.02mmol) , 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at a reaction temperature of 120 °C for 18 h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: diethyl ether=8 : 1), the product is a yellow solid, the melting point is 190-191° C., the yield is 60%, and the weight of the product is 40 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500MHz, DMSO-D6): δ 10.9 (s, 1H), 7.32-7.27 (m, 4H), 7.21-7.18 (m, 1H), 4.03 (t, J=4.70Hz, 4H), 3.57(t, J=4.70Hz, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125MHz, DMSO-D6): δ 170.4, 167.5, 150.7, 132.7, 129.4, 128.2, 126.0, 85.5, 66.1, 48.0;

HRMS (ESI): _calcd for _C14H14N2O3Se [ _M +H] ⁺ _339.0249 , found 339.0251.

Example 11

Synthesis of 1-Phenyl-3-Mormorpholinyl-4-Phenylselenomaleimide Compounds

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-phenylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv), acetic acid Copper (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at 120 °C for 18 h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: diethyl ether=8 : 1), the product was a yellow liquid, the yield was 81%, and the weight of the product was 67 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.46-7.43 (m, 2H), 7.40-7.32 (m, 5H), 7.29-7.21 (m, 3H), 4.19 (t, J=4.70 Hz, 4H) , 3.69(t, J=4.70Hz, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125MHz, CDCl ₃ ): δ 169.1, 165.5, 149.2, 131.9, 131.8, 129.9, 129.5, 128.9, 127.7, 126.9, 126.3, 88.5, 66.9, 48.7;

HRMS (ESI): _calcd for _C20H18N2O3Se [ _M +H] ⁺ _415.0562 , found 415.0567.

Example 12

Synthesis of 1-benzyl-3-morpholinyl-4-phenylselenomaleimide compounds

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-benzylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv), acetic acid Copper (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at 120 °C for 18 h at the reaction temperature. The reaction mixture was cooled, then ethyl acetate was added for dilution, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted with ethyl acetate three times, and combined. To the organic phase, add 5g of anhydrous sodium sulfate, stand still for 30min, wash the filter cake three times with 5mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether:diethyl ether=8 : 1), the product was a yellow liquid, the yield was 81%, and the weight of the product was 69 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.41-7.39 (m, 2H), 7.36-7.22 (m, 8H), 4.72 (s, 2H), 4.16 (t, J=4.70 Hz, 4H), 3.66 (t, J=4.70Hz, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.0, 166.3, 149.7, 136.5, 132.3, 129.5, 129.4, 128.6, 128.6, 127.7, 126.7, 87.2, 66.9, 48.5, 42.1;

HRMS (ESI): _calcd for _C21H20N2O3Se [ _M +H] ⁺ _429.0718 , found 429.0719.

Example 13

Synthesis of 1-cyclohexyl-3-morpholinyl-4-phenylselenomaleimide compounds

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-cyclohexylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv), acetic acid Copper (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at 120 °C for 18 h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 83%, and the weight of the product was 70 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.30-7.28 (m, 2H), 7.26-7.23 (m, 2H), 7.19 (t, J=7.0 Hz, 1H), 4.11 (t, J=4.70 Hz) , 4H), 3.96 (tt, J=8.3, 3.4Hz, 1H), 3.66 (t, J=4.70Hz, 4H), 2.10-2.03 (m, 2H), 1.82 (d, J=3.1Hz, 2H) , 1.68-1.66 (m, 2H), 1.34-1.18 (m, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.2, 166.4, 149.5, 132.4, 129.4, 129.3, 126.6, 87.6, 66.9, 51.4, 48.4, 29.9, 26.0, 25.2;

HRMS (ESI): calcd for C20H24N2O3Se[ _{M +} H] ⁺ _421.1031 , found _421.1033 .

Example 14

Synthesis of 1-(2-Thienylmethyl)-3-morpholinyl-4-phenylselenomaleimide Compounds

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-(2-thienylmethyl)maleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5 equiv), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times at a reaction temperature of 120 °C Stir for 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: diethyl ether=8 : 1), the product was a yellow solid, melting point: 58-59° C., yield 82%, and product weight was 71 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.30-7.28 (m, 2H), 7.26-7.19 (m, 4H), 7.08 (d, J=3.0 Hz, 1H), 6.94-6.92 (m, 1H) , 4.87(s, 2H), 4.13(t, J=4.70Hz, 4H), 3.63(t, J=4.70Hz, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 169.5, 165.9, 149.6, 138.3, 132.2, 129.5, 129.4, 127.6, 126.8, 126.7, 125.7, 87.3, 66.9, 48.5, 36.2;

HRMS (ESI): _calcd for _{C19H18N2O3SSe} [ _M +H] ⁺ _435.0282 , found 435.0288.

Example 15

Synthesis of 1-Methyl-3-morpholinyl-4-phenylselenomaleimide

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), morpholine (0.3mmol, 1.5equiv), acetic acid Copper (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, and stirred at 120 °C for 18 h at the reaction temperature. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: diethyl ether=8 : 1), the product was a yellow liquid, the yield was 85%, and the weight of the product was 60 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.31-7.30 (m, 2H), 7.26-7.23 (m, 2H), 7.20 (t, J=7.0 Hz, 1H), 4.16 (t, J=4.70 Hz) , 4H), 3.66 (t, J=4.70Hz, 4H), 3.0 (s, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.4, 166.7, 149.8, 132.3, 129.4, 129.3, 126.7, 87.0, 66.9, 48.5, 24.4

HRMS (ESI): _calcd for _C15H16N2O3Se [ _M +H] ⁺ _353.0405 , found 353.0401.

Example 16

Synthesis of 1-Methyl-3-thiomorpholinyl-4-phenylselenomaleimide Compounds

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), thiomorpholine (0.3mmol, 1.5equiv) , copper acetate (0.02mmol, 0.1equiv), sodium carbonate (0.8mmol, 4equiv) and 1mL N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, stirred at 120 ° C reaction temperature for 18h . The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 77%, and the weight of the product was 56 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.31-7.30 (m, 2H), 7.26-7.23 (m, 2H), 7.21-7.18 (m, 1H), 4.35 (t, J=4.70 Hz, 4H) , 3.04(s, 3H), 2.69(t, J=4.70Hz, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.3, 166.7, 150.2, 132.4, 129.4, 129.4, 126.7, 87.6, 51.2, 28.1, 24.5;

HRMS (ESI): _calcd for _{C15H16N2O2SSe} [M ₊ H] ⁺ _369.0177 , found 369.0179.

Example 17

Synthesis of 1-Methyl-3-tetrahydropyrrolyl-4-phenylselenomaleimide Compounds

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), tetrahydropyrrole (0.3mmol, 1.5equiv), Copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen and replaced three times, and stirred at 120°C for 18 h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 74%, and the weight of the product was 50 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.31 (d, J=7.4 Hz, 2H), 7.22 (t, J=7.3 Hz, 2H), 7.15 (t, J=7.2 Hz, 1H), 4.03 ( t, J=6.8Hz, 4H), 3.06 (s, 3H), 1.90 (t, J=6.8Hz, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 171.4, 166.2, 149.9, 135.0, 129.2, 128.8, 126.1, 82.2, 51.4, 25.1, 24.3;

HRMS (ESI): _calcd for _C15H16N2O2Se [M ₊ H] ⁺ _337.0456 , found 337.0458.

Example 18

Synthesis of 1-Methyl-3-cycloheptamino-4-phenylselenomaleimide

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), cyclohexylimide (0.3mmol, 1.5equiv) , copper acetate (0.02mmol, 0.1equiv), sodium carbonate (0.8mmol, 4equiv) and 1mL N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, stirred at 120 ° C reaction temperature for 18h . The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 80%, and the weight of the product was 58 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.30 (d, J=7.7 Hz, 2H), 7.21 (t, J=7.3 Hz, 2H), 7.15 (t, J=7.2 Hz, 1H), 4.07 ( t, J=6.1Hz, 4H), 3.04 (s, 3H), 1.80-1.79 (m, 4H), 1.57-1.56 (m, 4H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.9, 166.2, 150.5, 134.2, 129.2, 128.8, 126.1, 82.7, 52.9, 28.4, 26.3, 24.4;

HRMS (ESI): _calcd for _C17H20N2O2Se [ _{M +} H] ⁺ 365.0769, found 365.0770.

Example 19

Synthesis of 1-methyl-3-(4-piperidinemethanol)-4-phenylselenomaleimide

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), 4-piperidinemethanol (0.3mmol, 1.5equiv) were mixed together ), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, stirring at a reaction temperature of 120 ° C 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 58%, and the weight of the product was 44 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.32-7.30 (m, 2H), 7.24-7.21 (m, 2H), 7.18-7.16 (m, 1H), 5.18 (d, J=13.3 Hz, 2H) , 3.46(d, J=5.9Hz, 2H), 3.04(s, 3H), 1.82-1.79(m, 3H), 1.64(s, 2H), 1.29-1.23(m, 3H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 170.7, 166.8, 150.9, 133.0, 129.3, 129.2, 126.4, 85.5, 67.1, 48.7, 38.1, 29.3, 24.4;

HRMS (ESI): _calcd for _C17H20N2O3Se [ _M +H] ⁺ _381.0718 , found 381.0721.

Example 20

Synthesis of 1-methyl-3-(4-piperidinecarboxymethyl)-4-phenylselenomaleimide

At room temperature, iodobenzene (0.6mmol, 3equiv), selenium powder (0.6mmol, 3equiv), N-methylmaleimide (0.2mmol, 1equiv), methyl 4-piperidinecarboxylate (0.3mmol, 1.5 equiv), copper acetate (0.02 mmol, 0.1 equiv), sodium carbonate (0.8 mmol, 4 equiv) and 1 mL of N,-methylpyrrolidone were added to the reaction tube, then filled with oxygen, and replaced three times, at a reaction temperature of 120 °C Stir for 18h. The reaction mixture was cooled, then diluted with ethyl acetate, the diluted solution was transferred to a separatory funnel, extracted with saturated brine, the aqueous phase and the organic phase were separated, and the aqueous phase was extracted three times with ethyl acetate, and the combined To the organic phase, add 5 g of anhydrous sodium sulfate, stand still for 30 min, wash the filter cake three times with 5 mL of ethyl acetate each time, then spin off the solvent, and separate the product by column chromatography (eluent: petroleum ether: ether=8 : 1), the product was a yellow liquid, the yield was 79%, and the weight of the product was 64 mg.

The data of the H NMR spectrum of the obtained product are as follows:

¹ H NMR (500 MHz, CDCl ₃ ): δ 7.32-7.30 (m, 2H), 7.24-7.22 (m, 2H), 7.19-7.17 (m, 1H), 4.87 (dt, J=13.6, 3.6 Hz, 2H), 3.68(s, 3H), 3.37-3.32(m, 2H), 3.04(s, 3H), 2.62-2.56(m, 1H), 1.97-1.94(m, 2H), 1,80-1.73( m, 2H);

The data of the carbon nuclear magnetic resonance spectrum of the obtained product are as follows:

¹³ C NMR (125 MHz, CDCl ₃ ): δ 174.2, 170.6, 166.7, 150.6, 132.7, 129.3, 129.3, 126.5, 86.4, 51.9, 47.9, 40.2, 28.5, 24.4;

HRMS (ESI): _calcd for _C18H20N2O4Se [ _M +H] ⁺ _409.0667 , found 409.0668.

It can be seen from the above examples 1-20 that when the method of the present invention is adopted, the 3-amino-4-arylselenylmaleimide compound can be obtained in high yield and high purity.

Examples 21-23

Except replacing the transition metal catalyst copper acetate with the following copper salts, respectively, Examples 21-23 were implemented in the same manner as in Example 1, and the yields of the copper salt compounds and corresponding products used are shown in Table 1 below. Show.

Table 1

As can be seen from the above table 1, when other copper salts are used, cuprous iodide can react smoothly but the yield of the product declines relatively large, and cupric chloride and cupric bromide cannot catalyze the reaction, thus proving that cupric acetate is the key factor for the success of this reaction and is the most effective for this reaction system.

Examples 24-37

Except that the organic solvent N-methylpyrrolidone in it was replaced with the following organic solvents, respectively, implementations 24-37 were implemented in the same manner as in Example 1, and the yields of the organic solvents used and the corresponding products were as follows in Table 2 shown.

Table 2

Numbering solvent Reaction yield (%) Example 24 dimethyl sulfoxide twenty four Example 25 N,N-Dimethylacetamide 19 Example 26 Dichloromethane not responding Example 27 Ethyl acetate not responding Example 28 Pyridine not responding Example 29 1,4-Dioxane not responding Example 30 1,2-Dichloroethane not responding Example 31 Acetonitrile not responding Example 32 Toluene not responding Example 33 tetrahydrofuran not responding Example 34 Ethanol not responding Example 35 carbon tetrachloride not responding Example 36 Chloroform not responding Example 37 n-butanol not responding

It can be seen from the above table 2 that when other organic solvents are used, except in the strong polar solvent dimethyl sulfoxide and N,N-dimethylacetamide can react, but the yield is still reduced; Polar or even weakly coordinating solvent conditions do not have any product. This proves that the appropriate choice of organic solvent has a significant, even decisive, effect on whether the reaction can proceed.

Examples 38-39

Except replacing the alkali sodium carbonate therein with the following inorganic bases, respectively, Examples 38-39 were implemented in the same manner as in Example 1, and the yields of the alkali compounds used and the corresponding products were shown in Table 3 below, It is proved that sodium carbonate is the key factor for the success of this reaction.

table 3

Numbering base Reaction yield (%) Example 38 Cesium carbonate not responding Example 39 Lithium carbonate not responding

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, but not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: It is still scientific research to modify the technical solutions recorded in the foregoing embodiments, or to make equivalent replacements for some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the technical solutions of the embodiments of the present invention. scope.

Claims (7)

1. a preparation method of 3-amino-4-arylselenyl maleimide compound, is characterized in that, in organic solvent, under oxygen condition, with the aromatic iodine having structure shown in formula (I) Compound, the selenium powder of the structure shown in formula (II), the maleimide of the structure shown in formula (III) and the secondary amine shown in the structure of formula (IV) are reaction raw materials, under the catalysis of transition metal copper, The 3-amino-4-arylselenylmaleimide compound of the structure represented by formula (V) is obtained by the oxidative coupling reaction of the carbon-carbon double bond in the maleimide structure.

Described aromatic iodide is iodobenzene, 1-iodonaphthalene, 4-methyliodobenzene, 4-fluoroiodobenzene, 4-chloroiodobenzene, 4-bromoiodobenzene, 4-nitroiodobenzene, 4-triiodobenzene Fluoromethyliodobenzene, 4-cyanoiodobenzene and 3-iodothiophene; Described maleimide is maleimide, N-phenylmaleimide, N-benzylmaleimide, N-cyclohexylmaleimide and N-(2- thienylmethyl)maleimide; The secondary amines are morpholine, thiomorpholine, tetrahydropyrrole, cyclohexylimine, 4-piperidine methanol and methyl 4-piperidine carboxylate; The copper catalyst is copper acetate; Described alkali is sodium carbonate; The organic solvent is N-methylpyrrolidone. 2 . The preparation method according to claim 1 , wherein, in terms of molar amount, the consumption of the copper catalyst is 1-15% of the consumption of the compound of formula (III). 3 . 3. The preparation method according to claim 1, wherein the amount of the base is 100-400% of the amount of the compound of the formula (III). 4. preparation method according to claim 1 is characterized in that: the aromatic iodide of the structure shown in the described (I), the selenophenol of the structure shown in the formula (II), the maleate of the structure shown in the formula (III) The molar ratio of the imide to the secondary amine represented by the structure of formula (IV) is 6:6:2:3. 5 . The preparation method according to claim 1 , wherein the temperature in the range is 100-120° C. 6 . 6. preparation method according to claim 1 is characterized in that, the time of described reaction is 14-18h. 7. preparation method as claimed in claim 1, is characterized in that: after reaction finishes, add extraction agent extraction after reaction liquid is cooled, separate out aqueous phase and organic phase, get the organic phase containing extraction agent and target product and use anhydrous Dry over sodium sulfate, concentrate under reduced pressure, and separate the concentrate by column chromatography, wherein the silica gel is 300-400 mesh silica gel, and a mixture of petroleum ether and ether in a volume ratio of 95:5 is used as the eluent, and the eluent is collected and evaporated by rotary evaporation. After solvent, the 3-amino-4-arylselenylmaleimide compound represented by formula (V) is obtained.