N-amino hydrazone derivatives and processes for their preparation

Abstract

This invention belongs to the field of organic chemical synthesis technology, specifically relating to an N-aminohydrazone derivative and its preparation method. The N-aminohydrazone derivative has the general structural formulas I and II, where Formula I is [formula missing], and Formula II is [formula missing], wherein Ar- is phenyl, substituted phenyl, aryl, or heteroaryl; in Formula I, the two R'; together constitute morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative; in Formula II, R'; is morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative; R" is ethyl, isopropyl, tert-butyl, or benzyl; and R';';'; is H or phenyl. Formula I is prepared using aldehyde hydrazone compounds and azodicarboxylic acid ester compounds as reactants, employing a "one-pot two-step" method. Using aldehyde hydrazone compounds and azodicarboxylic acid ester compounds as reactants, a photocatalyst and a metal catalyst are added to the reaction system to prepare Formula II. The N-aminohydrazone derivative provided by this invention has a novel structure, good functional group compatibility, mild preparation conditions, and simple operation.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, specifically relating to an N-aminohydrazone derivative and its preparation method. Background Technology

[0002] Compounds with heterocyclic skeletons in their molecular structure have extremely wide applications in natural products, as well as in artificially synthesized drugs and functional materials, making them a class of compounds with significant research value and application prospects. Among the many heterocyclic compounds, nitrogen-containing heterocyclic compounds, with their unique physicochemical properties and excellent biological activities, exhibit extremely high research value in the field of medicinal chemistry, and their efficient synthetic methods have long been one of the core focuses of synthetic chemists.

[0003] The structures of common amidohydrazone compounds are as follows: .

[0004] Currently, there are several main methods for synthesizing amidohydrazone compounds: The first method is the traditional nitrile addition method, which involves the addition reaction of nitrile compounds with hydrazine under specific conditions to prepare amidohydrazone compounds, which are then derived. However, the core drawback of this method is that the reaction conditions are extremely harsh. The reaction requires extreme conditions such as high temperature, high pressure or strong acid and alkali environments. This not only places extremely high demands on the corrosion resistance and pressure resistance of the reaction equipment, increasing the equipment cost and operation difficulty, but also easily triggers side reactions, resulting in reduced product purity and poor yield. The second synthetic method is the coupling reaction of halohydrazones with nitrogen nucleophiles. This method is a relatively mild synthetic route, preparing the target product through the coupling reaction of halohydrazones with nitrogen nucleophiles. However, its prominent drawback is that a halogen group needs to be pre-introduced into the hydrazone substrate before the reaction, increasing the reaction steps and prolonging the synthesis cycle. Furthermore, the introduction of halogen groups increases reaction costs, and halogen reagents are usually toxic and corrosive, posing potential health hazards to operators and causing environmental pollution, which is inconsistent with the trend of green synthesis. In addition, this method has poor functional group compatibility; the introduction of halogen groups may damage the target functional groups. The third synthetic method is photocatalytic or electrochemical oxidative coupling, a novel synthetic route discovered in recent years. It prepares amidine hydrazones by oxidative coupling of aldehyde-derived hydrazones with nitrogen nucleophiles under photocatalytic or electrochemical conditions. However, the nucleophiles for this strategy are currently limited to heterocyclic compounds.

[0005] CN101012203A discloses an aminohydrazone derivative and its preparation method, clearly stating that the structure of the aminohydrazone derivative contains key functional groups such as hydrazone and amino groups, making it suitable for the synthesis of pharmaceutical intermediates and fine chemical products. The disclosed preparation method uses hydrazine compounds and carbonyl compounds as raw materials to prepare the target aminohydrazone derivative through a condensation reaction. The reaction requires specific catalysts and solvents, which to some extent improves the synthesis technology of aminohydrazone derivatives and fully reflects the research value and application potential of this type of compound. However, the reaction process involves a large amount of catalyst, a long reaction time, and cumbersome product separation and purification steps, resulting in low reaction efficiency and high production costs. Furthermore, the method has limited functional group compatibility. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to overcome the above-mentioned defects of the prior art and provide an N-aminohydrazone derivative and its preparation method. The derivative has a novel structure and good functional group compatibility. Its preparation conditions are mild, the operation is simple, green and environmentally friendly and the yield is high. The method does not require the pre-introduction of halogen groups or complex catalyst systems. It can efficiently prepare two types of N-aminohydrazone derivatives with different structures, while reducing the synthesis cost and environmental burden, and meeting the synthesis needs of pharmaceutical intermediates and fine chemical products.

[0007] The N-aminohydrazone derivatives described in this invention have general structural formulas of Formula I and Formula II, where Formula I is... Formula II is Wherein, Ar- is phenyl, substituted phenyl, aryl, or heteroaryl; the substituted phenyl is substituted by one or more substituents selected from methyl, ethyl, tert-butyl, methoxy, dimethylamino, phenyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, and cyano; the aryl is biphenyl-4-yl, naphthyl-2-yl, or 2,3-dihydrobenzofuran-5-yl; the heteroaryl is pyridin-2-yl, thiophene-2-yl, or benzo[b]thiophene-3-yl; In Formula I and Formula II, R'' represents ethyl, isopropyl, tert-butyl, or benzyl. In Formula I, the two R's together constitute a morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative; In Formula II, R' is morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative, and R''' is H or phenyl. When R' is morpholino or piperidin-1-yl, R''' is H; when R' is 2-phenylhydrazine derivative, R''' is phenyl.

[0008] The specific steps for preparing the N-aminohydrazone derivative of formula I are as follows: using aldehyde hydrazone compounds and azodicarboxylic acid ester compounds as reactants, adding solvent and heating the reaction, and after the reaction is completed, post-treatment is performed to obtain the target product of formula I.

[0009] The preparation of Formula I utilizes an aldehyde hydrazone as a nucleophile to nucleophilically attack azodicarboxylic acid esters, and then obtains N-aminoamidinium hydrazones, i.e., the target product Formula I, through electron and proton transfer processes.

[0010] The reaction formula of Formula I is: .

[0011] The reaction mechanism of Formula I is as follows: First, due to the electron-rich carbon-nitrogen double bond of the aldehyde hydrazone compound, it can act as a nucleophile to nucleophilically attack the nitrogen-nitrogen double bond of the azodicarboxylic acid ester compound, yielding a coupled intermediate. This intermediate then undergoes electron and proton transfer processes to obtain the target product, as shown below: .

[0012] In the preparation method of the N-aminohydrazone derivative of formula I, the aldehyde hydrazone compound is one of the following substances: (E)-N-morpholino-1-(p-tolyl)methylimine, (E)-N-morpholino-1-phenylmethylimine, (E)-1-(4-methoxyphenyl)-N-morpholinomethylimine, (E)-N,N-dimethyl-4-((morpholinoimino)methyl)aniline, (E)-1-(4-ethylphenyl)-N-morpholinomethylimine, (E)-1-(4-tert-butylphenyl)-N-morpholino Methylimine, (E)-1-([1,1'-biphenyl]-4-yl)-N-morpholinylmethyleneimine, (E)-1-(4-fluorophenyl)-N-morpholinylmethyleneimine, (E)-1-(4-chlorophenyl)-N-morpholinylmethyleneimine, (E)-1-(4-bromophenyl)-N-morpholinylmethyleneimine, (E)-1-(4-iodophenyl)-N-morpholinylmethyleneimine, (E)-N-morpholinyl-1-(4-trifluoromethylphenyl)methylimine, (E)-N-morpholinyl-1-(4-nitrophenyl)methylimine Amines, (E)-4-((morpholinylimino)methyl)benzonitrile, (E)-1-(2-methoxyphenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(o-tolyl)methylimine, (E)-1-(3-methoxyphenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(m-tolyl)methylimine, (E)-1-(3-bromophenyl)-N-morpholinylmethylimine, (E)-1-(3,5-dimethylphenyl)-N-morpholinylmethylimine, (E)-N- Morpholin-1-(pyridin-2-yl)methylimine, (E)-N-morpholin-1-(thiophen-2-yl)methylimine, (E)-1-(benzo[b]thiophen-3-yl)-N-morpholinomethylimine, (E)-1-(2,3-dihydrobenzofuran-5-yl)-N-morpholinomethylimine, (E)-N-morpholin-1-(naphth-2-yl)methylimine, (E)-N-(piperidin-1-yl)-1-(p-tolyl)methylimine, (E)-1-(4-methylbenzylene)-2-phenylhydrazine.

[0013] In the preparation method of the N-aminohydrazone derivative of formula I, the solvent is acetonitrile, the molar ratio of aldehyde hydrazone compound to azodicarboxylic acid ester compound is 1:2; the molar ratio of aldehyde hydrazone compound to solvent is 1 mol: 10~20 L; and the reaction temperature is 55℃.

[0014] The N-aminohydrazone derivative of formula I comprises: (Z)-1-((morpholinylimino)(p-tolyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(phenyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-methoxyphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-dimethylaminophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-ethylphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-tert-butylphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((1,1';[-biphenyl]-4-yl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-fluorophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-chlorophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-bromophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-iodophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(4-trifluoromethylphenyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)- 1-((morpholinylimino)(4-nitrophenyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((4-cyanophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((2-methoxyphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(o-tolyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((3-methoxyphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(m-tolyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z) -1-((3-bromophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((3,5-dimethylphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(pyridin-2-yl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(thiophen-2-yl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-(benzo[b]thiophen-3-yl(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((2,3-dihydrobenzofuran-5-yl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(naphth-2-yl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((morpholinylimino)(p-tolyl)methyl)azodicarboxylic acid diisopropyl ester, (Z)-1-((morpholinylimino)(p-tolyl)methyl)azodicarboxylic acid ditert-butyl ester, (Z)-1-((morpholinylimino)(p-tolyl)methyl)azodicarboxylic acid dibenzyl ester, (Z)-1-((piperidin-1-ylimino)(p-tolyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, (Z)-1-((2-phenylhydrazine))(p-tolyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester;

[0015] The specific steps for preparing the N-aminohydrazone derivative of formula II are as follows: using a "one-pot two-step" method, aldehyde hydrazone compounds and azodicarboxylic acid ester compounds are used as raw materials, solvent is added and heated to react, after the reaction, a photocatalyst and a metal catalyst are added to the reaction system, and further oxidation is carried out under blue light irradiation. After the reaction is completed, the target product of formula II is obtained through post-treatment.

[0016] Formula II uses a "one-pot, two-step" method to process the reaction: after the aldehyde hydrazone and azodicarboxylic acid ester compound are heated to obtain the corresponding N-aminoamidinium hydrazone compound, the reaction is not further processed. A photocatalyst and a metal catalyst are directly added, and oxygen is used as the oxidant. Under blue light irradiation, the N-aminoamidinium compound is further oxidized to obtain the corresponding N-aminoamidinium cyclized product, which is the target product Formula II.

[0017] The reaction formula for formula II is: .

[0018] Formula II, taking (E)-N-morpholino-1-(p-tolyl)methylimine as an example, has the following reaction mechanism: After the photocatalyst is excited, it abstracts electrons from the nitrogen atom of the morpholino ring, making it an amino cationic radical intermediate. Following electron and proton transfer, a carbon radical intermediate is obtained. This intermediate is oxidized by oxygen in the air or by excess azodicarboxylic acid esters remaining from the previous step, and then cyclized under the action of nickel ions to obtain the final target product, such as... Figure 122 As shown.

[0019] In the preparation method of the N-aminohydrazone derivative of formula II, the aldehyde hydrazone compound is one of the following substances: (E)-N-(4-methylmethylene)morpholin-4-amine, (E)-N-morpholinyl-1-(p-tolyl)methylimine, (E)-1-(4-methoxyphenyl)-N-morpholinylmethylimine, (E)-1-(4-ethylphenyl)-N-morpholinylmethylimine, (E)-1-(4-tert-butylphenyl)-N-morpholinylmethylimine, ( E)-1-([1,1'-biphenyl]-4-yl)-N-morpholinylmethylimine, (E)-1-(4-fluorophenyl)-N-morpholinylmethylimine, (E)-1-(4-chlorophenyl)-N-morpholinylmethylimine, (E)-1-(4-bromophenyl)-N-morpholinylmethylimine, (E)-1-(4-iodophenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(4-trifluoromethylphenyl)methylimine, (E)-N-morpholinyl-1-(4-nitrophenyl)methylimine, ( E)-4-((morpholinylimino)methyl)benzonitrile, (E)-1-(2-methoxyphenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(o-tolyl)methylimine, (E)-1-(2-fluorophenyl)-N-morpholinylmethylimine, (E)-1-(3-methoxyphenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(m-tolyl)methylimine, (E)-1-(3-bromophenyl)-N-morpholinylmethylimine, (E)-1-(3,5- (E)-N-morpholinomethylimine, (E)-N-morpholino-1-(thiophen-2-yl)methylimine, (E)-1-(benzo[b]thiophen-3-yl)-N-morpholinomethylimine, (E)-1-(2,3-dihydrobenzofuran-5-yl)-N-morpholinomethylimine, (E)-N-morpholino-1-(naphth-2-yl)methylimine, (E)-N-(piperidin-1-yl)-1-(p-tolyl)methylimine, (E)-1-(4-methylbenzylene)-2-phenylhydrazine.

[0020] In the preparation method of the N-aminohydrazone derivative of formula II, the photocatalyst is 9-mesinetrimethyl-10-methylacridinium tetrafluoroborate (Mes-Acr). + BF4 - The metal catalyst is nickel acetate tetrahydrate (Ni(OAc)2·4H2O).

[0021] In the preparation method of the N-aminohydrazone derivative of formula II, an aldehyde hydrazone compound and an azodicarboxylic acid ester compound in a molar ratio of 1:2 are used as raw materials. Acetonitrile is added as a solvent and the mixture is heated to 55°C for 10 hours. The molar volume ratio of the aldehyde hydrazone compound to the solvent is 1 mol: 10-20 L. After the reaction, a photocatalyst and a metal catalyst are added to the reaction system, and the mixture is further oxidized under blue light irradiation. The visible light wavelength of the reaction is 410 nm, the reaction temperature is 25°C, and the reaction time is 10-12 hours. The oxidant used is oxygen. The molar amount of the photocatalyst is 2 mol% of the aldehyde hydrazone compound, and the molar amount of the metal catalyst is 5 mol% of the aldehyde hydrazone compound.

[0022] The N-aminohydrazone derivative of formula II is: 3-(p-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazinro[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-phenyl-6,7,9,9a-tetrahydro-[1,4]oxazinro[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-methoxyphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazinro[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-ethylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazinro[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-ethylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazinro[4,3-b][ [1,2,4,5]Tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-tert-butylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-([1,1'-biphenyl]-4-yl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-fluorophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-chlorophenyl)-6,7,9,9a -Tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-bromophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-iodophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(4-trifluoromethylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(4 3-(4-cyanophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(2-methoxyphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(o-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(o-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(o-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester,Diethyl 2-dicarboxylate, 3-(2-fluorophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylate, 3-(3-methoxyphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylate, 3-(m-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylate, 3-(3-bromophenyl)- 6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(3,5-dimethylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(thiophen-2-yl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraazahexacyclic-1,2-dicarboxylic acid diethyl ester, 3-(benzo[b]thiophen-3 ... Hydrogen-[1,4]oxazinro[4,3-b][1,2,4,5]tetraazine six-membered heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(2,3-dihydrobenzofuran-5-yl)-6,7,9,9a-tetrahydro-[1,4]oxazinro[4,3-b][1,2,4,5]tetraazine six-membered heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(naphthyl-2-yl)-6,7,9,9a-tetrahydro-[1,4]oxazinro[4,3-b][1,2,4,5]tetraazine six-membered heterocyclic-1,2-dicarboxylic acid diethyl ester, 3-(p-tolyl ... [3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diisopropyl ester, 3-(p-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid dibenzyl ester, 3-(p-tolyl)-7,8,9,9a-tetrahydro-2H-pyrido[1,2-b][1,2,4,5]tetraazine hexacyclic heterocyclic-1,2(6H)-dicarboxylic acid diethyl ester, 4-benzyl-3-phenyl-6-(p-tolyl)-3,4-dihydro-1,2,4,5-tetraazine hexacyclic heterocyclic-1,2-dicarboxylic acid diethyl ester.

[0023] In the preparation methods of the N-aminohydrazone derivatives of Formula I and Formula II, the azodicarboxylic acid ester compound is one of the following substances: diethyl azodicarboxylate, diisopropyl azodicarboxylate, ditert-butyl azodicarboxylate, or dibenzyl azodicarboxylate.

[0024] In the preparation methods of the N-aminohydrazone derivatives of formulas I and II, after the reaction is completed, the reaction system is first quenched with water, then extracted with dichloromethane, and then dried with anhydrous Na2SO4, purified by vacuum distillation and column chromatography.

[0025] The method for synthesizing the N-aminohydrazone derivative of formula I of the present invention uses aldehyde hydrazone and azodicarboxylic acid ester as reactants, reacts them under heating conditions with acetonitrile as solvent, and then separates and purifies to obtain N-aminoamidinium hydrazone compounds.

[0026] The synthesis method of the N-aminohydrazone derivative of formula II of the present invention uses a "one-pot two-step" method to process the reaction: after the aldehyde hydrazone and azodicarboxylic acid ester compound are heated to obtain the corresponding N-aminoamidinium hydrazone compound, the reaction is not further processed. A photocatalyst and a metal catalyst are directly added, and oxygen is used as the oxidant. Under blue light irradiation, the N-aminoamidinium compound is further oxidized to obtain the corresponding N-aminoamidinium cyclized product.

[0027] This invention achieves highly efficient coupling of aldehyde hydrazones with azodicarboxylic acid esters under thermochemical conditions. The hydrogen substitution reaction on the hydrazone carbon can be successfully completed without the need for photochemical, electrochemical, or additional oxidants. The novel reaction pathway overcomes the technical limitations of existing hydrazone modification methods that rely on special catalytic or oxidation systems. The overall reaction conditions are mild and relaxed, eliminating the need for harsh reaction conditions such as high temperature, high pressure, strong acids, and strong bases, significantly improving experimental safety while reducing energy consumption and equipment requirements. The experimental process is simple and easy to control, effectively solving the problems of cumbersome operation and high reaction risk in traditional synthetic methods. This invention employs a two-step cascade reaction strategy, first constructing the amination product through thermochemical coupling, and then achieving intramolecular cyclization through photocatalysis combined with metal catalysis, oxygen oxidation, and blue light irradiation, precisely constructing the CN bond. The reaction exhibits high selectivity and has significant application value. The synthetic process is highly efficient and green, with a simple reaction system and low difficulty in product separation and purification, effectively avoiding the pain points of difficult product separation and numerous impurities in complex synthetic processes. Furthermore, the reaction has high atom economy, meeting the requirements of green and efficient development in modern organic synthesis. With good substrate applicability and functional group tolerance, and relying on a mild thermochemical and photochemical synergistic reaction system, a series of N-aminohydrazone derivatives and cyclized products can be synthesized efficiently. The broad substrate scope provides a universal and reliable new method for the preparation of functional molecules containing hydrazone skeletons. The synthetic route is simple and efficient, yielding high-value target products in just two steps, eliminating the need for complex intermediate preparation and multi-step transformations. This significantly shortens the synthesis cycle, improves preparation efficiency, and possesses excellent potential for scientific research applications and industrial transformation.

[0028] Compared with the prior art, the beneficial effects of the present invention are: (1) This invention provides two novel N-aminohydrazone derivatives, which enrich the types of amidohydrazone compounds. Their structures contain a variety of active functional groups, which are suitable for the synthesis of pharmaceutical intermediates and fine chemical products and have broad application prospects.

[0029] (2) The preparation method of the present invention is mild and simple, without the need for extreme reaction conditions such as high temperature, high pressure, strong acid and alkali, and without the need to introduce halogen groups into the hydrazone substrate in advance, thus avoiding the toxicity, corrosiveness and environmental pollution problems caused by halogen reagents, which is in line with the trend of green synthesis. At the same time, the reaction uses acetonitrile as a solvent, which is widely available and inexpensive, further reducing the synthesis cost.

[0030] (3) The preparation method of the present invention has good functional group compatibility and can be adapted to a variety of substituted phenyl, aryl and heteroaryl substituted aldehyde hydrazone raw materials. It can efficiently prepare a variety of target products, and the product separation and purification steps are simple, with high yield and purity. Formula II adopts the "one pot two steps" method, which does not require separation of intermediate products, shortens the synthesis cycle, improves reaction efficiency and reduces operation difficulty. Attached Figure Description

[0031] Figure 1 This is the hydrogen NMR spectrum of the product from Example 1 of the present invention; Figure 2 This is the carbon NMR spectrum of the product from Example 1 of the present invention; Figure 3 This is the hydrogen NMR spectrum of the product from Example 2 of the present invention; Figure 4 This is the carbon NMR spectrum of the product from Example 2 of the present invention; Figure 5 This is the hydrogen NMR spectrum of the product from Example 3 of the present invention; Figure 6 This is the carbon NMR spectrum of the product from Example 3 of the present invention; Figure 7 The hydrogen NMR spectrum of the product in Example 4 of this invention; Figure 8 This is the carbon NMR spectrum of the product from Example 4 of the present invention; Figure 9 This is the hydrogen NMR spectrum of the product from Example 5 of the present invention; Figure 10 This is the carbon NMR spectrum of the product from Example 5 of the present invention; Figure 11 The hydrogen NMR spectrum of the product in Example 6 of this invention; Figure 12 The carbon NMR spectrum of the product in Example 6 of this invention; Figure 13 The hydrogen NMR spectrum of the product in Example 7 of this invention; Figure 14The carbon NMR spectrum of the product in Example 7 of this invention; Figure 15 The hydrogen NMR spectrum of the product in Example 8 of this invention; Figure 16 The carbon NMR spectrum of the product in Example 8 of this invention; Figure 17 The NMR fluorine spectrum of the product in Example 8 of this invention; Figure 18 The hydrogen NMR spectrum of the product of Example 9 of this invention; Figure 19 The carbon NMR spectrum of the product of Example 9 of this invention; Figure 20 The hydrogen NMR spectrum of the product of Example 10 of this invention; Figure 21 The image shows the carbon NMR spectrum of the product from Example 10 of this invention. Figure 22 The hydrogen NMR spectrum of the product of Example 11 of this invention; Figure 23 The carbon NMR spectrum of the product of Example 11 of this invention; Figure 24 The hydrogen NMR spectrum of the product in Example 12 of this invention; Figure 25 The carbon NMR spectrum of the product in Example 12 of this invention; Figure 26 The NMR fluorine spectrum of the product from Example 12 of this invention; Figure 27 The hydrogen NMR spectrum of the product in Example 13 of this invention; Figure 28 The carbon NMR spectrum of the product in Example 13 of this invention; Figure 29 The hydrogen NMR spectrum of the product in Example 14 of this invention; Figure 30 The carbon NMR spectrum of the product in Example 14 of this invention; Figure 31 The hydrogen NMR spectrum of the product of Example 15 of this invention; Figure 32 The carbon NMR spectrum of the product in Example 15 of this invention; Figure 33 The hydrogen NMR spectrum of the product in Example 16 of this invention; Figure 34 The image shows the carbon NMR spectrum of the product from Example 16 of this invention. Figure 35 The hydrogen NMR spectrum of the product in Example 17 of this invention; Figure 36 The carbon NMR spectrum of the product in Example 17 of this invention; Figure 37 The hydrogen NMR spectrum of the product of Example 18 of this invention; Figure 38 The carbon NMR spectrum of the product of Example 18 of this invention; Figure 39 The hydrogen NMR spectrum of the product of Example 19 of this invention; Figure 40 The carbon NMR spectrum of the product of Example 19 of this invention; Figure 41 The hydrogen NMR spectrum of the product of Example 20 of this invention; Figure 42 The carbon NMR spectrum of the product in Example 20 of this invention; Figure 43 The hydrogen NMR spectrum of the product of Example 21 of this invention; Figure 44 The image shows the carbon NMR spectrum of the product from Example 21 of this invention. Figure 45 The hydrogen NMR spectrum of the product of Example 22 of this invention; Figure 46 The carbon NMR spectrum of the product of Example 22 of this invention; Figure 47 The hydrogen NMR spectrum of the product in Example 23 of this invention; Figure 48 The carbon NMR spectrum of the product in Example 23 of this invention; Figure 49 The hydrogen NMR spectrum of the product of Example 24 of this invention; Figure 50 The carbon NMR spectrum of the product in Example 24 of this invention; Figure 51 The hydrogen NMR spectrum of the product from Example 25 of this invention; Figure 52 The carbon NMR spectrum of the product of Example 25 of this invention; Figure 53 The hydrogen NMR spectrum of the product of Example 26 of this invention; Figure 54 The carbon NMR spectrum of the product of Example 26 of this invention; Figure 55 The hydrogen NMR spectrum of the product of Example 27 of this invention; Figure 56 The carbon NMR spectrum of the product in Example 27 of this invention; Figure 57 The hydrogen NMR spectrum of the product of Example 28 of this invention; Figure 58 The carbon NMR spectrum of the product of Example 28 of this invention; Figure 59 The hydrogen NMR spectrum of the product of Example 29 of this invention; Figure 60 The carbon NMR spectrum of the product of Example 29 of this invention; Figure 61 The hydrogen NMR spectrum of the product of Example 30 of this invention; Figure 62 The image shows the carbon NMR spectrum of the product from Example 30 of this invention. Figure 63 The hydrogen NMR spectrum of the product of Example 31 of this invention; Figure 64 The carbon NMR spectrum of the product of Example 31 of this invention; Figure 65 The hydrogen NMR spectrum of the product of Example 32 of this invention; Figure 66 The carbon NMR spectrum of the product of Example 32 of this invention; Figure 67 The hydrogen NMR spectrum of the product of Example 33 of this invention; Figure 68 The carbon NMR spectrum of the product of Example 33 of this invention; Figure 69 The hydrogen NMR spectrum of the product of Example 34 of this invention; Figure 70 The carbon NMR spectrum of the product of Example 34 of this invention; Figure 71 The hydrogen NMR spectrum of the product of Example 35 of this invention; Figure 72 The carbon NMR spectrum of the product of Example 35 of this invention; Figure 73 The hydrogen NMR spectrum of the product of Example 36 of this invention; Figure 74 The carbon NMR spectrum of the product of Example 36 of this invention; Figure 75 The hydrogen NMR spectrum of the product of Example 37 of this invention; Figure 76 The carbon NMR spectrum of the product of Example 37 of this invention; Figure 77 The NMR fluorine spectrum of the product from Example 37 of this invention; Figure 78 The hydrogen NMR spectrum of the product of Example 38 of this invention; Figure 79 The carbon NMR spectrum of the product of Example 38 of this invention; Figure 80 The hydrogen NMR spectrum of the product of Example 39 of this invention; Figure 81 The carbon NMR spectrum of the product of Example 39 of this invention; Figure 82The hydrogen NMR spectrum of the product of Example 40 of this invention; Figure 83 The carbon NMR spectrum of the product of Example 40 of this invention; Figure 84 The hydrogen NMR spectrum of the product of Example 41 of this invention; Figure 85 The carbon NMR spectrum of the product of Example 41 of this invention; Figure 86 The NMR fluorine spectrum of the product from Example 41 of this invention; Figure 87 The hydrogen NMR spectrum of the product of Example 42 of this invention; Figure 88 The carbon NMR spectrum of the product of Example 42 of this invention; Figure 89 The hydrogen NMR spectrum of the product of Example 43 of this invention; Figure 90 The carbon NMR spectrum of the product of Example 43 of this invention; Figure 91 The hydrogen NMR spectrum of the product of Example 44 of this invention; Figure 92 The carbon NMR spectrum of the product of Example 44 of this invention; Figure 93 The hydrogen NMR spectrum of the product of Example 45 of this invention; Figure 94 The carbon NMR spectrum of the product of Example 45 of this invention; Figure 95 The hydrogen NMR spectrum of the product of Example 46 of this invention; Figure 96 The carbon NMR spectrum of the product of Example 46 of this invention; Figure 97 The NMR fluorine spectrum of the product from Example 46 of this invention; Figure 98 The hydrogen NMR spectrum of the product of Example 47 of this invention; Figure 99 The carbon NMR spectrum of the product of Example 47 of this invention; Figure 100 The hydrogen NMR spectrum of the product of Example 48 of this invention; Figure 101 The carbon NMR spectrum of the product of Example 48 of this invention; Figure 102 The hydrogen NMR spectrum of the product of Example 49 of this invention; Figure 103 The carbon NMR spectrum of the product of Example 49 of this invention; Figure 104 This is the hydrogen NMR spectrum of the product from Example 50 of the present invention; Figure 105 The image shows the carbon NMR spectrum of the product from Example 50 of this invention. Figure 106 The hydrogen NMR spectrum of the product of Example 51 of this invention; Figure 107 The image shows the carbon NMR spectrum of the product from Example 51 of this invention. Figure 108 The hydrogen NMR spectrum of the product of Example 52 of this invention; Figure 109 The carbon NMR spectrum of the product of Example 52 of this invention; Figure 110 The hydrogen NMR spectrum of the product of Example 53 of this invention; Figure 111 The carbon NMR spectrum of the product of Example 53 of this invention; Figure 112 The hydrogen NMR spectrum of the product of Example 54 of this invention; Figure 113 The carbon NMR spectrum of the product of Example 54 of this invention; Figure 114 The hydrogen NMR spectrum of the product of Example 55 of this invention; Figure 115 This is the carbon NMR spectrum of the product from Example 55 of the present invention; Figure 116 The hydrogen NMR spectrum of the product of Example 56 of this invention; Figure 117 The carbon NMR spectrum of the product of Example 56 of this invention; Figure 118 The hydrogen NMR spectrum of the product of Example 57 of this invention; Figure 119 The carbon NMR spectrum of the product of Example 57 of this invention; Figure 120 The hydrogen NMR spectrum of the product of Example 58 of this invention; Figure 121 The carbon NMR spectrum of the product of Example 58 of this invention; Figure 122 The reaction mechanism diagram of Formula II of the present invention is shown. Detailed Implementation

[0032] The present invention will be further described below with reference to specific embodiments.

[0033] The aldehydes, hydrazines, azo dyes, and Ni(OAc)₂·4H₂O used in the examples were all purchased from Anhui Zesheng Technology Co., Ltd. (Annaiji). Mes-Acr + BF4 -The photocatalyst (9-trimethyl-10-methylacridinium tetrafluoroborate) was purchased from Shanghai Haohong Biomedical Technology Co., Ltd. All aldehyde hydrazone compounds used were prepared using existing technologies (Electrochemical CH Sulfonylation of Hydrazones, Organic Letters, 2024, 25, 3440-3444.). Example 1

[0034] In this embodiment, diethyl (Z)-1-((morpholinylimino)(p-tolyl)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps are as follows: (E)-N-(4-methylmethylene)morpholin-4-amine (0.2 mmol) and diethyl azodicarbonate (0.4 mmol) were stirred in 2 mL of acetonitrile at 55 °C for 10 h. The reaction was monitored by thin-layer chromatography until (E)-N-(4-methylmethylene)morpholin-4-amine was completely consumed. The reaction was then quenched with water and extracted with dichloromethane (3 times × 20 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography to obtain (Z)-1-((morpholinylimino)(p-tolyl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester, weighing 69.5 mg, with a yield of 92% and a purity ≥95%. The 1H and 1C spectra are as follows. Figure 1-2 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 7.90 (d, J = 7.8 Hz, 2H), 7.18 (d, J =8.0 Hz, 2H), 4.21 (q, J = 7.1 Hz, 2H), 4.09 (q, J = 7.1 Hz, 2H), 3.90-3.80 (m, 4H), 2.95-2.82 (m, 4H), 2.36 (s, 3H), 1.29 (t, J = 7.2 Hz, 3H), 1.03 (t, J = 7.0 Hz, 3H).

[0035] 13 C NMR (101 MHz, CDCl3) δ 155.7, 154.1, 153.8, 141.3, 130.9, 129.0, 128.3, 66.3, 66.1, 63.2, 62.3, 54.9, 21.5, 14.5, 14.1.

[0036] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 27 N4O5 + 379.1981; found 379.1966. Example 2

[0037] In this embodiment, diethyl (Z)-1-((morpholinylimino)(phenyl)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-phenylmethyleneimine.

[0038] The target product weighed 66.3 mg, with a yield of 91% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 3-4 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.02 (d, J = 7.5 Hz, 2H), 7.40 (dt,J = 14.6, 7.0 Hz, 3H), 4.23 (q, J = 7.1 Hz, 2H), 4.09 (q, J = 7.1 Hz,2H), 3.90 - 3.83(m, 4H), 2.97-2.89 (m, 4H), 1.30 (t, J = 7.1 Hz, 3H), 1.00(t, J = 7.1 Hz, 3H).

[0039] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.77, 133.8, 130.9, 128.3, 128.3, 66.4, 66.1, 63., 62.38, 55.0, 54.8, 14.5, 14.0.

[0040] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 25 N4O5 + 365.1825; found 365.1809. Example 3

[0041] In this embodiment, diethyl (Z)-1-((4-methoxyphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-methoxyphenyl)-N-morpholinylmethylimine.

[0042] The target product weighed 73.3 mg, with a yield of 93% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 5-6 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.98 (d, J = 7.8 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 4.21 (q, J = 7.1 Hz, 2H), 4.10 (q, J = 7.1 Hz, 2H), 3.86(t, J = 4.7 Hz, 4H), 3.82 (s, 3H), 2.88 (t, J = 4.6 Hz, 4H), 1.29 (t, J = 7.2Hz, 3H), 1.06(d, J = 7.3 Hz, 3H).

[0043] 13 C NMR (101 MHz, CDCl3) δ 162.0, 155.8, 154.2, 153.8, 130.1, 126.1, 113.7, 66.4, 63.2, 62.3, 55.4, 54.9, 14.5, 14.1.

[0044] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 27 N4O6 + 395.1931; found 395.1913. Example 4

[0045] In this embodiment, diethyl (Z)-1-((4-dimethylaminophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N,N-dimethyl-4-((morpholinylimino)methyl)aniline.

[0046] The target product weighed 67.6 mg, with a yield of 83% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 7-8 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.90 (d, J = 7.3Hz, 2H), 6.65(d, J = 8.7 Hz, 2H), 4.20 (q, J = 7.2 Hz, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.88-3.81 (m, 4H), 2.99 (s, 6H), 2.88-2.82 (m, 4H), 1.28 (t, J = 7.1 Hz, 3H), 1.08 (t, J = 7.2 Hz, 3H).

[0047] 13 C NMR (101 MHz, CDCl3) δ 155.8, 155.2, 154.2,152.5, 129.8, 120.6,111.4, 66.5, 63.0, 62.2, 55.1, 40.2, 14.5, 14.3.

[0048] HRMS (ESI) m / z: [M+H] + calcd for C 10 H 30 N5O5 + 408.224; found 408.2231. Example 5

[0049] In this embodiment, diethyl (Z)-1-((4-ethylphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-ethylphenyl)-N-morpholinylmethylimine.

[0050] The target product weighed 69.8 mg, with a yield of 89% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 9-10As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 7.93 (d, J = 7.8 Hz, 2H), 7.20 (d, J = 8.1Hz, 2H), 4.21 (q, J = 7.2 Hz, 2H), 4.09 (q, J = 7.0 Hz, 2H), 3.90-3.82 (m, 4H), 2.93-2.85 (m, 4H), 2.66 (q, J = 7.6 Hz, 2H), 1.29 (t, J = 7.2Hz, 3H), 1.21 (t, J =7.6 Hz, 3H), 1.03 (d, J = 7.1 Hz, 3H).

[0051] 13 C NMR (101 MHz, CDCl3) δ 155.7,154.1, 153.8, 147.6, 131.1, 128.4,127.9, 66.4, 63.2, 62.3, 54.9, 28.8, 15.4, 14.5, 14.1.

[0052] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 29 N4O5 + 393.2138; found 393.2120. Example 6

[0053] In this embodiment, diethyl (Z)-1-((4-tert-butylphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-tert-butylphenyl)-N-morpholinomethylimine.

[0054] The target product weighed 71.4 mg, with a yield of 85% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 11-12 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 7.94 (d, J = 8.1 Hz, 2H), 7.40 (d, J = 8.3 Hz, 2H), 4.22 (q, J = 7.1 Hz, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.90-3.83(m, 4H), 2.94-2.87 (m, 4H), 1.31 (s, 9H), 1.28 (d, J = 7.1 Hz, 3H), 1.02 (t, J = 6.0Hz, 3H).

[0055] 13 C NMR (101 MHz, CDCl3) δ 155.7, 154.4, 154.0, 153.8, 130.8, 128.1, 125.3, 66.4, 63.2, 62.3, 54.9, 34.8, 31.2, 14.5, 14.0.

[0056] HRMS (ESI) m / z: [M+H] + calcd for C 21 H 33 N4O5 + 421.2451; found 421.2463. Example 7

[0057] In this embodiment, diethyl (Z)-1-(([1,1';-biphenyl]-4-yl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-([1,1'-biphenyl]-4-yl)-N-morpholinylmethylimine.

[0058] The target product weighed 80.1 mg, with a yield of 91% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 13-14 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 8.10 (d, J = 8.0 Hz, 2H), 7.66- 7.58 (m, 4H), 7.45 (t, J = 7.5 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 4.24 (q,J= 7.1 Hz, 2H), 4.13 (q, J = 6.5, 5.9 Hz, 2H), 3.92-3.84 (m, 4H), 2.99-2.90(m,4H), 1.31 (t, J = 7.2 Hz, 3H), 1.07 (d, J = 7.0 Hz, 3H).

[0059] 13 C NMR (101 MHz, CDCl3) δ 155.8, 153.8, 153.5, 143.6, 140.4, 132.7,128.9, 128.8, 127.8, 127.2,127.0, 66.4, 63.3, 62.4, 54.9, 14.5, 14.1.

[0060] HRMS (ESI) m / z: [M+H] + calcd for C 23 H 29 N4O5 + 441.2138; found 441.2122. Example 8

[0061] In this embodiment, diethyl (Z)-1-((4-fluorophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-fluorophenyl)-N-morpholinylmethylimine.

[0062] The target product weighed 67.3 mg, with a yield of 88% and a purity ≥95%. The proton, carbon, and fluorine spectra were as follows: Figure 15-17 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 8.08-7.98 (m, 2H), 7.06 (t, J=8.7 Hz, 2H), 4.22 (q, J = 7.1 Hz, 2H), 4.10 (q, J = 7.1 Hz, 2H), 3.89-3.80(m, 4H), 2.93-2.85 (m, 4H), 1.29 (t, J = 7.1 Hz, 3H), 1.05 (d, J = 7.0 Hz, 3H).

[0063] 13 C NMR (101 MHz, CDCl3) δ 165.9, 163.4, 155.7, 153.6, 130.6, 130.5, 115.5, 115.2, 66.3, 63.3, 62.4, 54.8, 29.6, 14.4, 14.1.

[0064] 9 F NMR (376 MHz, CDCl3) δ -109.43.

[0065] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 24 FN4O5 + 383.1731; found383.1713. Example 9

[0066] In this embodiment, diethyl (Z)-1-((4-chlorophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-chlorophenyl)-N-morpholinylmethylimine.

[0067] The target product weighed 71.7 mg, with a yield of 90% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 18-19 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 7.97 (d, J = 8.2 Hz, 2H), 7.35 (d, J =8.6 Hz, 2H), 4.22 (q, J = 7.1 Hz, 2H), 4.15-4.07 (m, 2H), 3.90-3.82(m, 4H), 2.94-2.87 (m, 4H), 1.29 (t, J = 7.2 Hz, 3H), 1.06 (d, J = 6.9 Hz, 3H).

[0068] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.5, 137.0, 132.4, 129.6, 128.5,128.4, 66.3, 63.4,62.5, 54.8, 14.4, 14.1.

[0069] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 24 ClN4O5 + 399.1435; found 399.1422. Example 10

[0070] In this embodiment, diethyl (Z)-1-((4-bromophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-bromophenyl)-N-morpholinylmethylimine.

[0071] The target product weighed 81.3 mg, with a yield of 92% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 20-21 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 7.90 (d, J = 8.2 Hz, 2H), 7.51 (d, J= 8.6 Hz, 2H), 4.22 (q, J = 7.1 Hz, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.89-3.81 (m,4H), 2.95-2.87 (m, 4H), 1.29 (t, J = 7.1 Hz, 3H), 1.06 (t, J = 7.2Hz, 3H).

[0072] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.5, 132.8, 131.5, 129.9, 125.5, 66.3, 63.4, 62.5, 54.8, 14.5, 14.1, 1.0.

[0073] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 24 BrN4O5 + 443.0930; found 443.0914. Example 11

[0074] In this embodiment, diethyl (Z)-1-((4-iodophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-iodophenyl)-N-morpholinylmethylimine.

[0075] The target product weighed 83.3 mg, with a yield of 85% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 22-23 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.79-7.67 (m, 4H), 4.22 (q, J= 7.0Hz, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.86 (t, J = 4.7 Hz, 4H), 2.91 (t, J = 4.7 Hz, 4H), 1.29 (t, J = 7.1 Hz, 3H), 1.07 (d, J = 7.0 Hz, 3H).

[0076] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.5, 137.5, 133.4, 129.9, 97.7, 66.3, 63.4, 62.5, 54.7, 29.6, 14.5, 14.1.

[0077] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 24 IN4O5 + 491.0791; found 491.0772. Example 12

[0078] In this embodiment, diethyl (Z)-1-((morpholinylimino)(4-trifluoromethylphenyl)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(4-trifluoromethylphenyl)methylimine.

[0079] The target product weighed 80.4 mg, with a yield of 93% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 24-26 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 8.13 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H), 4.22 (q, J = 7.1 Hz, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.90-3.82 (m, 4H), 2.99-2.91 (m, 4H), 1.29 (t, J = 7.1 Hz, 3H), 1.03 (t, J =7.1 Hz, 3H).

[0080] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.4, 151.3, 137.4, 132.5, 132.1,128.5, 125.2, 125.2, 125.2, 125.1, 122.6, 66.3, 63.5, 62.5, 54.7,14.4,14.0.

[0081] 9 F NMR (376 MHz, CDCl3) δ -62.84.

[0082] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 24 F3N4O5 + 433.1699; found 433.1688. Example 13

[0083] In this embodiment, diethyl (Z)-1-((morpholinylimino)(4-nitrophenyl)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(4-nitrophenyl)methylimine.

[0084] The target product weighed 58.9 mg, with a yield of 72% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 27-28 As shown, where: 1H NMR (400 MHz, CDCl3) δ8.19 (q, J = 8.7 Hz, 5H), 4.22 (q, J = 7.3Hz,2H), 4.12 (q, J = 7.1 Hz, 2H), 3.90-3.84 (m, 4H), 3.02-2.95 (m, 4H), 1.29 (t, J = 7.1 Hz, 3H), 1.07 (d, J = 7.2 Hz, 3H).

[0085] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.4, 149.0, 140.1, 129.0, 123.4, 66.3, 63.7, 62.7, 55.2, 54.6, 14.4, 14.1.

[0086] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 24 N5O7 + 410.1676; found 410.1648. Example 14

[0087] In this embodiment, diethyl (Z)-1-((4-cyanophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-4-((morpholinylimino)methyl)benzonitrile.

[0088] The weight was 73.2 mg, the yield was 94%, the purity was ≥95%, and the proton and carbon spectra were as follows. Figures 29-30 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.29 (s, 1H), 8.12 (s, 2H), 7.65 (d, J= 7.3Hz, 2H), 4.21 (q, J = 6.6, 6.1 Hz, 2H), 4.11 (q, J = 7.0 Hz, 2H), 3.90-3.80(m, 4H), 3.00-2.88 (m, 4H), 1.28 (t, J = 6.5 Hz, 3H), 1.03 (d, J = 7.5 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.3, 138.4, 132.0, 128.7, 118.5,113.8,66.2, 63.6, 62.6, 54.6, 14.4, 14.1. HRMS (ESI) m / z: [M+H] + calcd for C 18 H 24 N5O5 + 390.1777; found 390.1760. Example 15

[0089] In this embodiment, diethyl (Z)-1-((2-methoxyphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(2-methoxyphenyl)-N-morpholinylmethylimine.

[0090] The target product weighed 70.2 mg, with a yield of 89% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 31-32 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.60 (d, J = 6.4 Hz, 2H), 7.28 (t,J = 8.0 Hz, 1H), 7.00 - 6.93 (m, 1H), 4.21 (q, J = 7.1 Hz, 2H), 4.09 (q, J = 7.1 Hz, 2H), 3.88 - 3.84 (m, 4H), 3.83 (s, 3H), 2.94 - 2.88 (m, 4H), 1.28 (t, J = 7.1 Hz, 3H), 1.02 (t, J = 6.9 Hz, 3H).

[0091] 13 C NMR (101 MHz, CDCl3) δ 159.6, 155.7,153.7, 153.5, 135.2, 129.3,120.9, 117.2, 113.1, 66.3, 63.2, 62.3, 55.4, 54.8, 14.5, 14.1.

[0092] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 27 N4O6 + 395.1931; found 395.1914. Example 16

[0093] In this embodiment, diethyl (Z)-1-((morpholinylimino)(o-tolyl)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(o-tolyl)methylimine.

[0094] The target product weighed 61.3 mg, with a yield of 81% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 33-34 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 8.06 (s, 1H), 7.30 - 7.18 (m,4H), 4.26 (q, J= 7.1 Hz, 2H), 4.03 (q, J = 7.1 Hz, 2H), 3.91-3.85 (m, 4H), 2.99-2.93 (m, 4H), 2.51 (s, 3H), 1.31 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.1Hz, 3H).

[0095] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.3, 152.7, 138.1, 133.5, 131.0,129.7, 129.6, 125.9, 66.4,63.2, 62.4, 55.0, 20.8, 14.5, 13.8.

[0096] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 27 N4O5 + 379.1981; found 379.1964. Example 17

[0097] In this embodiment, diethyl (Z)-1-((3-methoxyphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(3-methoxyphenyl)-N-morpholinylmethylimine.

[0098] The target product weighed 73.3 mg, with a yield of 93% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 35-36 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 7.61 (d, J = 6.5 Hz, 2H), 7.29 (t, J = 8.1 Hz, 1H), 6.98 (d, J = 7.1 Hz, 1H), 4.22 (q, J = 7.1 Hz, 2H), 4.10 (q, J = 7.1, 5.8 Hz, 2H), 3.89-3.85 (m, 4H), 3.84 (s, 3H), 2.95-2.88 (m, 4H).

[0099] 13 C NMR (101 MHz, CDCl3) δ 159.6, 155.7, 153.7, 153.6, 135.2, 129.3,120.9, 117.3, 113.1, 66.4,63.2, 62.4, 55.4, 54.8, 14.5, 14.1.

[0100] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 27 N4O6 + 395.1931; found 395.1931. Example 18

[0101] In this embodiment, diethyl (Z)-1-((morpholinylimino)(m-tolyl)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(m-tolyl)methylimine. The target product weighed 69.6 mg, with a yield of 92% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 37-38 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.81 (d, J = 21.4 Hz, 2H), 7.27 (q,J = 7.4 Hz, 2H), 4.23 (q, J = 7.1 Hz, 2H), 4.10 (q, J = 7.1 Hz, 2H), 3.91 - 3.83 (m,4H), 2.95 - 2.89 (m, 4H), 2.38 (s, 3H), 1.30 (t, J = 7.1 Hz,3H), 1.03 (d, J = 6.8 Hz,3H).

[0102] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.7, 137.9, 133.7, 131.8, 128.7,128.2, 125.7, 66.4, 63.2, 62.3, 54.8, 21.4, 14.5, 14.1.

[0103] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 27 N4O5 + 379.1981; found 379.1964. Example 19

[0104] In this embodiment, diethyl (Z)-1-((3-bromophenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(3-bromophenyl)-N-morpholinylmethylimine.

[0105] The target product weighed 75.1 mg, with a yield of 89% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 39-40 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.56 (d,J = 8.0 Hz, 1H), 7.26 (t, J = 7.9 Hz, 1H), 4.23 (q, J = 6.5, 6.0 Hz,2H), 4.12 (q, J = 7.1Hz, 2H), 3.89-3.83 (m, 4H), 2.96-2.89 (m, 4H), 1.31 (t,J = 7.0 Hz, 3H), 1.06(d, J = 7.0 Hz, 3H).

[0106] 13 C NMR (101 MHz, CDCl3) δ 155.6, 153.5, 151.7,136.0, 133.7, 131.0,129.8, 127.0, 122.3, 66.3, 63.4, 62.5, 54.7, 14.5, 14.1.

[0107] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 24 BrN4O5 + 443.0930; found 443.0913. Example 20

[0108] In this embodiment, diethyl (Z)-1-((3,5-dimethylphenyl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(3,5-dimethylphenyl)-N-morpholinylmethylimine.

[0109] The target product weighed 67.5 mg, with a yield of 86% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 41-42 As shown, where: 1H NMR (400 MHz, CDCl3) δ8.45 (s, 1H), 7.23 (s, 2H), 6.54 (t, J = 2.3Hz, 1H), 4.22 (q,J = 7.1 Hz, 2H), 4.12 (q, J = 7.1 Hz, 2H), 2.95-2.88 (m,4H), 1.29 (t, J = 7.2 Hz,3H), 1.06 (t, J = 7.1 Hz, 3H).

[0110] 13 C NMR (101 MHz, CDCl3) δ 160.7, 155.6,153.7, 153.5, 135.8, 106.2,103.7, 66.4, 63.3, 62.4, 55.5, 54.8, 14.5, 14.2.

[0111] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 27 N4O5 + 391.1981; found 391.1963. Example 21

[0112] In this embodiment, diethyl (Z)-1-((morpholinylimino)(pyridin-2-yl)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(pyridin-2-yl)methylimine.

[0113] The target product weighed 54.1 mg, with a yield of 74% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 43-44 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 4.9 Hz, 1H), 7.89 (d, J = 8.1Hz, 1H), 7.64 (td, J = 7.8,1.8 Hz, 2H), 7.15 (ddd, J = 7.5, 4.9, 1.2 Hz, 1H), 4.24-4.14 (m, 4H), 3.85 (t, J =4.7 Hz, 4H), 3.75 (s, 4H), 1.26 (t, J = 7.0Hz, 3H), 1.18 (d, J = 7.3 Hz, 3H).

[0114] 13 C NMR (101 MHz, CDCl3) δ 156.8, 156.0, 153.2, 148.3, 136.5, 122.5,121.1, 66.8,63.2, 61.9, 54.2, 14.5, 14.4.

[0115] HRMS (ESI) m / z: [M+H] + calcd for C 16 H 24 N5O5 + 366.1777; found 366.1761. Example 22

[0116] In this embodiment, diethyl (Z)-1-((morpholinylimino)(thiophen-2-yl)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(thiophen-2-yl)methylimine.

[0117] The target product weighed 62.2 mg, with a yield of 84% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 45-46 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.75 (s, 1H), 7.36 (d, J = 5.1Hz, 1H), 7.05-7.01 (m, 1H), 4.22-4.15 (m, 4H), 3.86-3.80 (m, 4H), 2.93-2.87 (m,4H), 1.30-1.26 (m, 3H), 1.12 (t, J = 7.3 Hz, 3H).

[0118] 13 C NMR (101 MHz, CDCl3) δ 155.5, 153.9, 148.9, 137.2, 131.1, 129.4,127.5, 66.3, 63.4, 62.4,54.9, 14.4, 14.2.

[0119] HRMS (ESI) m / z: [M+H] + calcd for C 15 H 23 N4O5S + 371.1389; found371.1371. Example 23

[0120] In this embodiment, diethyl (Z)-1-(benzo[b]thiophene-3-yl(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(benzo[b]thiophen-3-yl)-N-morpholinylmethylimine.

[0121] The target product weighed 64.7 mg, with a yield of 77% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 47-48 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.1 Hz, 2H), 8.25 (s, 1H), 7.85 (d, J = 7.9 Hz, 1H), 7.42 (dt, J = 28.7, 7.4 Hz, 2H), 4.24 (q, J = 7.3 Hz,2H), 4.12 (q, J= 7.1 Hz, 2H), 3.94-3.86 (m, 4H), 3.00 (t, J = 4.7 Hz, 4H), 1.30 (t, J = 7.1 Hz,3H), 1.02 (t, J = 7.1 Hz, 3H).

[0122] 13 C NMR (101 MHz, CDCl3) δ 155.8, 154.0,149.8, 140.8, 136.5, 134.3,129.7, 125.1, 125.0, 124.9, 122.6, 66.3, 63.2, 62.4, 55.3,14.5,14.2.

[0123] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 25 N4O5S + 421.1546; found421.1535. Example 24

[0124] In this embodiment, diethyl (Z)-1-((2,3-dihydrobenzofuran-5-yl)(morpholinylimino)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(2,3-dihydrobenzofuran-5-yl)-N-morpholinylmethylimine.

[0125] The target product weighed 72.3 mg, with a yield of 89% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 49-50 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 7.86 (d, J = 12.9 Hz, 2H), 6.77 (d, J = 8.4 Hz, 1H), 4.60 (t, J = 8.7 Hz, 2H), 4.21 (d, J = 13.8 Hz, 2H),4.12(q, J = 7.1 Hz, 2H), 3.86 (t, J = 4.8 Hz, 4H), 3.22 (t, J = 8.7 Hz, 2H),2.87 (t, J = 4.5Hz, 4H), 1.29 (t, J = 7.6 Hz, 3H), 1.07 (d, J = 7.4 Hz, 3H).

[0126] 13 C NMR (101 MHz, CDCl3) δ 162.9, 155.8, 153.9, 129.6, 127.3, 126.1,125.2, 109.1, 71.9, 66.4,63.1, 62.3, 55.0, 29.3, 14.5, 14.4, 14.2.

[0127] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 27 N4O6 + 407.1931; found 407.1912. Example 25

[0128] In this embodiment, diethyl (Z)-1-((morpholinylimino)(naphth-2-yl)methyl)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(naphth-2-yl)methylimine.

[0129] The target product weighed 70.4 mg, with a yield of 85% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 51-52 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.55 (s, 1H), 8.10 (d, J = 8.6Hz,1H), 7.93 (d, J = 7.4 Hz, 1H), 7.84 (d, J = 8.6 Hz, 2H), 7.55-7.45 (m,2H), 4.25 (q,J = 7.1 Hz, 2H), 4.09 (q, J = 7.1 Hz, 2H), 3.95 - 3.85 (m, 4H),3.03-2.93 (m,4H), 1.32 (t, J = 5.9 Hz, 3H), 0.97 (t, J = 7.4 Hz, 3H).

[0130] 13 C NMR (101 MHz, CDCl3) δ 155.7, 153.9, 153.7, 134.7, 132.9, 131.1,129.1, 128.9, 128.0,127.7, 127.2, 126.3, 125.0, 66.4, 63.3, 62.4, 54.9, 14.5,14.1.

[0131] HRMS (ESI) m / z: [M+H] + calcd for C 21 H 27 N4O5 + 415.1981; found 415.1961. Example 26

[0132] In this embodiment, diisopropyl (Z)-1-((morpholinylimino)(p-tolyl)methyl)azodicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that diethyl azodicarboxylate is replaced with an equimolar amount of diisopropyl azodicarboxylate.

[0133] The target product weighed 69.5 mg, with a yield of 92% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 53-54 As shown, where: 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 7.90 (d, J = 7.8 Hz, 2H), 7.18(d, J = 7.9Hz, 2H), 4.99 (q, J = 6.3 Hz, 1H), 4.85 (p, J = 6.2 Hz, 1H), 3.89-3.83 (m, 4H), 2.92-2.86 (m, 4H), 2.37 (s, 3H), 1.28 (q, J = 8.1, 7.3 Hz, 6H), 1.02 (s, 6H).

[0134] 13 C NMR (101 MHz, CDCl3) δ 155.3, 154.3, 153.3, 141.1, 131.2, 128.9, 128.4, 71.2, 70.2, 66.4, 54.8, 22.0, 21.5, 21.5.

[0135] HRMS (ESI) m / z: [M+H] + calcd for C 20 H 29 N4O5 + 405.2138; found 405.2121. Example 27

[0136] In this embodiment, di-tert-butyl (Z)-1-((morpholinylimino)(p-tolyl)methyl)azodicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that diethyl azodicarboxylate is replaced with an equimolar amount of ditert-butyl azodicarboxylate.

[0137] The target product weighed 46.0 mg, with a yield of 53% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 55-56 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 7.90 (d, J = 7.6 Hz, 2H), 7.18(d, J = 7.9 Hz, 2H), 3.91-3.81 (m, 4H), 2.89 (t, J = 4.7 Hz, 4H), 2.37 (s, 3H), 1.49 (s, 9H), 1.21 (s, 9H).

[0138] 13 C NMR (101 MHz, CDCl3) δ 154.6, 152.2, 140.9, 128.9, 128.4, 82.9, 81.6, 66.4, 54.8, 28.3, 28.2, 27.9, 27.8, 21.5.

[0139] HRMS (ESI) m / z: [M+H] + calcd for C 22 H 33 N4O5 + 435.2607; found 435.2631. Example 28

[0140] In this embodiment, dibenzyl (Z)-1-((morpholinylimino)(p-tolyl)methyl)azodicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that diethyl azodicarboxylate is replaced with an equimolar amount of dibenzyl azodicarboxylate.

[0141] The target product weighed 77.3 mg, with a yield of 77% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 57-58 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 7.89 (s, 2H), 7.34 (s, 6H), 7.32 (s, 1H), 7.2-7.18 (m, 3H), 7.01 (d, J = 7.4 Hz, 2H), 5.18 (s, 2H), 5.07(s, 2H), 3.74 (t, J = 4.7Hz, 4H), 2.79 (t, J = 4.7 Hz, 4H), 2.36 (s, 3H).

[0142] 13 C NMR (101 MHz, CDCl3) δ 155.5, 153.9, 153.7, 141.4, 135.5, 135.0,130.6, 129.2, 128.6, 128.5, 128.4, 128.4,128.3, 128.2, 128.1, 68.7, 68.0, 66.3, 54.9, 21.5.

[0143] HRMS (ESI) m / z: [M+H] + calcd for C 28 H 29 N4O5 + 501.2138; found 501.2127. Example 29

[0144] In this embodiment, diethyl (Z)-1-((piperidin-1-ylimino)(p-tolyl)methyl)hydrazine-1,2-dicarboxylic acid ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-(piperidin-1-yl)-1-(p-tolyl)methylimine. The target product weighed 65.4 mg, with a yield of 85% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 59-60 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 9.08 (s, 1H), 7.88 (d, J = 7.8 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 4.18 (q, J = 7.1 Hz, 2H), 4.07 (q, J = 7.0 Hz, 2H), 2.79(t, J = 5.5Hz, 4H), 2.33 (s, 3H), 1.72 (p, J = 5.5 Hz, 4H), 1.49 (dd, J =8.1, 3.3 Hz, 2H), 1.26 (t,J = 7.1 Hz, 3H), 1.07 - 0.92 (m, 3H).

[0145] 13 C NMR (101 MHz, CDCl3) δ 156.0, 153.9, 140.9, 131.3, 128.9, 128.3, 62.9, 62.1, 55.8, 25.6, 23.7, 21.4, 14.5, 14.1.

[0146] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 29 N4O4 + 377,2189; found 377.2194. Example 30

[0147] In this embodiment, diethyl (Z)-1-((2-phenylhydrazine-1,2-dicarboxylic acid)hydrazine-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 1, except that (E)-N-(4-methylmethylene)morpholine-4-amine is replaced with an equimolar amount of (E)-1-(4-methylbenzyl)-2-phenylhydrazine.

[0148] The target product weighed 43.8 mg, with a yield of 57% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 61-62 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 7.45 (d, J = 8.1 Hz, 2H), 7.29 (t,J = 7.6 Hz, 2H), 7.24 (d, J = 7.8 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H),7.02 (s, 1H), 6.89(t, J = 7.0 Hz, 1H), 4.24 (dq, J = 21.1, 7.1 Hz, 4H), 2.37(s, 3H), 1.28 (t, J = 7.1 Hz,3H), 1.13 (t, J = 7.1 Hz, 3H).

[0149] 13 C NMR (101 MHz, CDCl3) δ 158.1, 155.4,144.3, 138.4, 131.6, 131.1,129.5, 129.2, 124.6, 120.4, 113.3, 63.8, 63.2, 21.3, 14.4.

[0150] HRMS (ESI) m / z: [M+H] + calcd for C 20 H 25 N4O4 + 385.1876; found 385.1855. Example 31

[0151] In this embodiment, 3-(p-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps are as follows: (E)-N-(4-methylmethylene)morpholin-4-amine (0.2 mmol) and diethyl azodicarbonate (0.4 mmol) were stirred in 2 mL of acetonitrile at 55 °C for 10 h, and the reaction was monitored by thin-layer chromatography until (E)-N-(4-methylmethylene)morpholin-4-amine was completely consumed. Then, Ni(OAc)₂·4H₂O (0.4 mmol) and Mes-Acr were added. + BF 4- (5%). The reaction was placed in an RLH-18CU8 photocatalytic reaction system and irradiated with a 410 nm light source at 25 °C for 10 h until (E)-N-(4-methylmethylene)morpholin-4-amine was completely consumed as detected by thin-layer chromatography. The reaction was then quenched with water and extracted with dichloromethane (3 times × 20 mL). The organic layers were combined, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography to give 61.7 mg of 3-(p-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraazacyclo-1,2-dicarboxylic acid diethyl ester, with a yield of 82% and a purity of ≥95%. The 1H and 1C spectra are as follows. Figures 63-64 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 7.8 Hz, 2H), 7.18 (d, J = 7.9Hz, 2H), 4.63 (d, J = 9.6 Hz, 1H), 4.30-4.08 (m, 5H), 3.91 (dd, J = 11.7, 3.3Hz, 1H), 3.75 (td, J = 11.6, 2.5 Hz, 1H), 3.59 (t, J = 10.2 Hz, 1H), 3.49 (d,J = 12.0 Hz, 1H), 3.35 (td, J = 11.9, 3.4 Hz, 1H), 2.37 (s, 3H), 1.32 (t, J =7.1 Hz, 3H), 1.12 (t, J = 7.1Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 155.4, 153.6, 140.4, 129.4, 129.1,126.4,75.3, 68.3, 66.2, 63.3, 63.2, 54.6, 21.5, 14.4, 14.1. HRMS (ESI) m / z: [M+H] + calcd forC 18 H 25 N4O5 + 377.1825; found 377.1816. Example 32

[0152] In this embodiment, 3-phenyl-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(p-tolyl)methylimine.

[0153] The target product weighed 56.4 mg, with a yield of 78% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 65-66 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 4.6 Hz, 2H), 7.41-7.34 (m, 3H), 4.70 (d, J = 8.9 Hz, 1H), 4.31-4.06 (m, 5H), 3.91 (dd, J = 11.6, 3.3 Hz, 1H), 3.74 (td, J =11.7, 2.5 Hz, 1H), 3.59 (t, J = 10.3 Hz, 1H), 3.52 (d, J = 12.0Hz, 1H), 3.37 (td, J =11.9, 3.4 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H), 1.09 (t, J= 7.1 Hz, 3H).

[0154] 13C NMR (101 MHz, CDCl3) δ 161.4, 155.4, 153.6, 128.1, 124.6, 113.9,75.9, 68.6, 66.4, 63.3,63.2, 55.4, 54.6, 14.4, 14.1.

[0155] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 23 N4O5 + 363.1668; found 363.1659. Example 33

[0156] In this embodiment, 3-(4-methoxyphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-methoxyphenyl)-N-morpholinylmethylimine.

[0157] The target product weighed 63.5 mg, with a yield of 81% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 67-68 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4 Hz, 2H), 6.90 (d,J = 8.8Hz, 2H), 4.57 (d, J = 9.5 Hz, 1H), 4.28-4.07 (m, 5H), 3.92 (dd, J = 11.5,3.2Hz, 1H), 3.83 (s, 3H), 3.75 (td, J = 11.7, 2.5 Hz, 1H), 3.59 (t, J = 10.2Hz, 1H), 3.47(d, J = 10.9 Hz, 1H), 3.32 (td, J = 11.9, 3.4 Hz, 1H), 1.31 (t,J = 7.1 Hz, 3H), 1.13 (t, J= 7.1 Hz, 3H).

[0158] 13C NMR (101 MHz, CDCl3) δ 161.4, 155.4, 153.6, 128.1, 124.6, 113.8, 75.9, 68.6, 66.4, 63.3, 63.2, 55.4, 54.6, 14.4, 14.1.

[0159] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 25 N4O6 + 393.1774; found 393.1764. Example 34

[0160] In this embodiment, 3-(4-ethylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-ethylphenyl)-N-morpholinylmethylimine.

[0161] The target product weighed 62.4 mg, with a yield of 80% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 69-70 As shown, where: 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.8 Hz, 2H), 7.20 (d, J =8.0Hz, 2H), 4.63 (d, J = 9.0 Hz, 1H), 4.23 (dt, J = 12.6, 6.8 Hz, 3H), 4.18-4.13(m,1H), 4.11 (dd, J = 10.6, 7.0 Hz, 1H), 3.91 (dd, J = 11.6, 3.3 Hz, 1H), 3.79-3.69 (m,1H), 3.58 (t, J = 10.2 Hz, 1H), 3.49 (d, J = 12.4 Hz, 1H), 3.34(td, J = 11.9, 3.4 Hz,1H), 2.66 (q, J = 7.6 Hz, 2H), 1.32 (t, J = 7.1 Hz,3H), 1.23 (t, J = 7.6 Hz, 3H), 1.11 (t,J = 7.1 Hz, 3H).

[0162] 13 C NMR (101 MHz, CDCl3) δ 155.4, 153.6, 146.7, 129.6, 127.9, 126.4, 75.3, 68.3, 66.2, 63.3, 63.2, 54.6, 28.8, 15.4, 14.4, 14.1.

[0163] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 27 N4O5 + 391.1981; found 391.1990. Example 35

[0164] In this embodiment, 3-(4-tert-butylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-tert-butylphenyl)-N-morpholinylmethylimine.

[0165] The target product weighed 64.4 mg, with a yield of 77% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 71-72 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.3Hz, 2H), 4.62 (d, J = 8.6 Hz, 1H), 4.24 (dtd, J = 10.7, 7.1, 3.5 Hz, 3H),4.20-4.07 (m, 2H), 3.91 (d, J = 14.2 Hz, 1H), 3.75 (td, J = 11.7, 2.4 Hz,1H), 3.58(t, J = 10.2 Hz, 1H), 3.50 (d, J = 11.1 Hz, 1H), 3.34 (td, J = 11.9,3.4 Hz, 1H), 1.35-1.30 (m, 12H), 1.12 (t, J = 7.1 Hz, 3H).

[0166] 13 C NMR (101 MHz, CDCl3) δ 155.4, 153.6, 153.5, 129.3, 126.2, 125.4,75.2, 68.3, 66.2, 63.3, 63.2, 54.6, 34.8, 31.2,14.4, 14.1.

[0167] HRMS (ESI) m / z: [M+H] + calcd for C 21 H 31 N4O5 + 419.2294; found419.2301. Example 36

[0168] In this embodiment, 3-([1,1'-biphenyl]-4-yl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-([1,1'-biphenyl]-4-yl)-N-morpholinylmethylimine.

[0169] The target product weighed 74.4 mg, with a yield of 85% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 73-74 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.0 Hz, 2H), 7.65-7.59 (m, 4H), 7.45 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.2 Hz, 1H), 4.70 (d, J = 9.4 Hz,1H),4.31-4.08 (m, 5H), 3.93 (dd, J = 11.6, 3.3 Hz, 1H), 3.77 (td, J = 11.7, 2.5Hz,1H), 3.61 (t, J = 10.3 Hz, 1H), 3.54 (d, J = 12.1 Hz, 1H), 3.39 (td, J =11.9, 3.4 Hz, 1H), 1.34 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H).

[0170] 13 C NMR (101 MHz, CDCl3) δ 155.4, 153.5, 142.8, 140.4, 131.1, 128.9,127.7, 127.1, 127.1, 126.8,75.0, 68.2, 66.2, 63.4, 63.3, 54.6, 29.7, 14.4,14.1.

[0171] HRMS (ESI) m / z: [M+H] + calcd for C 23 H 27 N4O5 + 439.1981; found 439.1962. Example 37

[0172] In this embodiment, 3-(4-fluorophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-fluorophenyl)-N-morpholinylmethylimine.

[0173] The target product weighed 60.1 mg, with a yield of 79% and a purity ≥95%. The proton, carbon, and fluorine spectra were as follows: Figures 75-77 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.87 - 7.73 (m, 2H), 7.06 (t, J = 8.7Hz,2H), 4.67 (d, J = 7.3 Hz, 1H), 4.31-4.05 (m, 5H), 90 (dd, J = 11.6, 3.2 Hz,1H),3.73 (td, J = 11.7, 2.5 Hz, 1H), 3.57 (t, J = 10.3 Hz, 1H), 3.50 (d, J =11.1 Hz, 1H),3.36 (td, J = 12.0, 3.4 Hz, 1H), 1.31 (t, J = 7.1 Hz, 3H), 1.12(t, J = 7.1 Hz, 3H).

[0174] 13 C NMR (101 MHz, CDCl3) δ 165.2, 162.7, 74.9, 155.3, 153.3, 128.5,128.5,128.4, 115.6, 115.4, 74.9, 68.1, 66.1, 63.4, 63.4, 54.6, 14.4, 14.1.

[0175] 19 F NMR (376 MHz, CDCl3) δ -110.33.

[0176] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 22 FN4O5 + 381.1574; found 381.1557. Example 38

[0177] In this embodiment, 3-(4-chlorophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-chlorophenyl)-N-morpholinylmethylimine.

[0178] The target product weighed 61.8 mg, with a yield of 78% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 78-79 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.3Hz, 2H), 4.70 (s, 1H), 4.33-4.18 (m, 3H), 4.18-4.06 (m, 2H), 3.91(dd, J =11.6, 3.3 Hz, 1H), 3.73 (t, J = 10.4 Hz, 1H), 3.57 (t, J = 10.3 Hz, 1H), 3.51(d, J = 11.0 Hz, 1H), 3.38 (td, J = 12.0, 3.4 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.1 Hz, 3H).

[0179] 13 C NMR (101 MHz, CDCl3) δ 168.9, 155.3, 153.3, 136.0, 130.9, 128.6, 127.6, 74.6, 68.0, 66.1, 63.5, 63.4, 54.6, 14.4, 14.1.

[0180] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 22 ClN4O5 + 397.1279; found 397.1260. Example 39

[0181] In this embodiment, 3-(4-bromophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-bromophenyl)-N-morpholinylmethylimine.

[0182] The target product weighed 75.7 mg, with a yield of 86% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 80-81 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 2H), 7.50 (d, J = 8.8Hz, 2H), 4.72 (d, J = 9.5 Hz, 1H), 4.23 (dt, J = 24.1, 7.0 Hz, 3H), 4.17-4.05(m, 2H),3.90 (dd, J = 11.6, 3.3 Hz, 1H), 3.72 (t, J = 11.7 Hz, 1H), 3.57 (t,J = 10.3 Hz, 1H),3.51 (d, J = 11.0 Hz, 1H), 3.37 (td, J = 12.0, 3.3 Hz, 1H),1.31 (t, J = 7.1 Hz, 3H),1.12 (t, J = 7.2 Hz, 3H).

[0183] 13 C NMR (101 MHz, CDCl3) δ 155.3, 153.3, 131.6,131.3, 128.6, 127.8,124.3, 74.5, 68.0, 66.0, 63.5, 63.4, 54.6, 14.4, 14.1.

[0184] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 22 BrN4O5 + 441.0774; found 441.0756. Example 40

[0185] In this embodiment, 3-(4-iodophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(4-iodophenyl)-N-morpholinylmethylimine.

[0186] The target product weighed 69.3 mg, with a yield of 71% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 82-83 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.1 Hz, 2H), 7.51 (d, J = 8.1Hz, 2H), 4.72 (d, J = 8.5 Hz, 1H), 4.30-4.16 (m, 3H), 4.12 (tt, J = 11.0, 5.0Hz, 2H), 3.89 (dd, J = 11.6, 3.3 Hz, 1H), 3.71 (t, J = 10.4 Hz, 1H), 3.56 (t,J = 10.3 Hz, 1H), 3.51 (d, J =13.2 Hz, 1H), 3.37 (td, J = 12.0, 3.3 Hz, 1H),1.31 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.1 Hz, 3H).

[0187] 13 C NMR (101 MHz, CDCl3) δ 155.4, 153.4, 137.7, 132.0, 128.0,96.4,74.5, 68.0, 66.2, 63.6, 63.5, 54.7, 51.9, 14.5, 14.2.

[0188] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 22 IN4O5 + 489.0635; found 489.0627. Example 41

[0189] In this embodiment, 3-(4-trifluoromethylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(4-trifluoromethylphenyl)methylimine.

[0190] The target product weighed 72.3 mg, with a yield of 84% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 84-86 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 8.0 Hz, 2H), 7.27 (d, J =8.1Hz, 2H), 4.48 (d, J = 9.4 Hz, 1H), 3.89 (ddd, J = 25.0, 11.4, 7.1 Hz, 3H),3.80-3.69(m, 2H), 3.54 (dd, J = 11.6, 3.3 Hz, 1H), 3.36 (t, J = 11.7 Hz, 1H),3.26 - 3.13 (m,2H), 3.07 (td, J = 12.1, 3.4 Hz, 1H), 0.97 (t, J = 7.1 Hz,3H), 0.76 (t, J = 7.1 Hz, 3H).

[0191] 13 C NMR (101 MHz, CDCl3) δ 155.3, 153.2, 135.9, 131.5, 131.2, 126.5,125.2,122.6, 73.5, 67.5, 65.8, 63.6, 63.5, 54.6, 14.4, 14.0.

[0192] 19 F NMR (376 MHz, CDCl3) δ -62.74.

[0193] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 22 F3N4O5 +431.1542; found 431.1563. Example 42

[0194] In this embodiment, 3-(4-nitrophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(4-nitrophenyl)methylimine.

[0195] The target product weighed 54.6 mg, with a yield of 67% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 87-88 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.8 Hz, 2H), 7.89 (d, J =8.4Hz, 2H), 4.95 (d, J = 8.9 Hz, 1H), 4.33-4.15 (m, 3H), 4.15-4.07 (m, 2H), 3.89(dd, J = 11.7, 3.1 Hz, 1H), 3.68 (td, J = 11.7, 2.5 Hz, 1H), 3.63-3.52 (m,2H), 3.48(td, J = 12.2, 3.3 Hz, 1H), 1.33 (t, J = 7.1 Hz, 3H), 1.13 (t, J =7.1 Hz, 3H).

[0196] 13 C NMR (101 MHz, CDCl3) δ 155.2, 153.0, 148.2, 138.6, 126.9, 126.2,123.6, 72.5,67.2, 65.7, 63.8, 63.7, 54.7, 14.4, 14.1.

[0197] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 22 N5O7 + 408.1519; found 408.1509. Example 43

[0198] In this embodiment, 3-(4-cyanophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-4-((morpholinylimino)methyl)benzonitrile.

[0199] The target product weighed 65.8 mg, with a yield of 85% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 89-90 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.0 Hz, 2H), 7.66 (d, J =8.2Hz, 2H), 4.90 (d, J = 10.6 Hz, 1H), 4.33 - 4.16 (m, 3H), 4.16 - 4.05 (m, 2H),3.89.

[0200] 13 C NMR (101 MHz, CDCl3) δ 155.2, 153.0, 136.8, 132.1, 126.7, 118.6,112.8, 67.3,65.8, 63.7, 63.7, 54.7, 14.4, 14.1.

[0201] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 22 N5O5 + 388.1621; found 388.1605. Example 44

[0202] In this embodiment, 3-(2-methoxyphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(2-methoxyphenyl)-N-morpholinylmethylimine.

[0203] The target product weighed 62.0 mg, with a yield of 79% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 91-92 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.44-7.33 (m, 2H), 7.28 (t, J = 7.9 Hz, 1H), 6.94 (dd, J = 7.2, 2.7 Hz, 1H), 4.73-4.62 (m, 1H), 4.32-4.19 (m, 3H), 4.19-4.07 (m,2H), 3.91 (dd, J = 11.6, 3.3 Hz, 1H), 3.83 (s, 3H), 3.74 (td, J =11.7, 2.5 Hz, 1H), 3.58(t, J = 10.3 Hz, 1H), 3.52 (d, J = 13.5 Hz, 1H), 3.37 (td, J = 12.0, 3.4 Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.1 Hz, 3H).

[0204] 13 C NMR (101 MHz, CDCl3) δ 159.7,155.3, 153.5, 133.6, 129.4, 119.1,117.0, 116.4, 111.2, 75.0, 68.2, 66.2, 63.4, 63.3,55.3, 54.6, 14.4, 14.1.

[0205] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 25 N4O6 + 393.1774; found 393.1756. Example 45

[0206] In this embodiment, 3-(o-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(o-tolyl)methylimine.

[0207] The target product weighed 55.0 mg, with a yield of 73% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 93-94 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.0 Hz, 1H), 7.27-7.22 (m, 1H), 7.20 (d, J = 7.0 Hz, 2H), 5.21 (s, 1H), 4.38-4.27 (m, 2H), 4.10 - 3.97 (m,3H), 3.76(dd, J = 11.5, 3.2 Hz, 1H), 3.66-3.53 (m, 3H), 3.52 - 3.44 (m, 1H),2.49 (s, 3H),1.35 (t, J = 7.1 Hz, 3H), 0.98 (t, J = 7.1 Hz, 3H).

[0208] 13 C NMR (101 MHz, CDCl3) δ 155.3, 152.6, 136.5, 133.3, 130.7, 128.9,128.7, 125.5, 64.4, 63.6,63.2, 54.3, 20.6, 14.4, 13.8.

[0209] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 25 N4O5 + 377.1835; found 377.1830. Example 46

[0210] In this embodiment, 3-(2-fluorophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(2-fluorophenyl)-N-morpholinylmethylimine.

[0211] The target product weighed 38.7 mg, with a yield of 51% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 95-97 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.60 (t, J = 7.6 Hz, 1H), 7.38-7.30 (m, 1H), 7.15 (t, J = 7.6 Hz, 1H), 7.11-7.03 (m, 1H), 5.24 (s, 1H), 4.30 (qd, J =7.1,4.3 Hz, 2H), 4.17-4.04 (m, 2H), 3.99 (dd, J = 11.0, 3.7 Hz, 1H), 3.75 (d, J =11.4 Hz, 1H), 3.65-3.47 (m, 4H), 1.34 (t, J = 7.1 Hz, 3H), 1.04 (t, J = 7.1Hz, 3H).

[0212] 13 C NMR (101 MHz, CDCl3) δ 161.2, 158.7, 155.4, 152.5, 130.8, 130.7,129.6, 123.8, 123.8, 122.1, 122.0, 116.1, 115.8, 64.6, 64.4, 63.6, 63.4,54.5, 14.3, 13.9.

[0213] 19 F NMR (376 MHz, CDCl3) δ -115.13.

[0214] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 22 FN4O5 + 381.1574; found 381.1580. Example 47

[0215] In this embodiment, 3-(3-methoxyphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(3-methoxyphenyl)-N-morpholinylmethylimine.

[0216] The target product weighed 62.7 mg, with a yield of 80% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 98-99 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.44 - 7.33 (m, 2H), 7.29 (t, J = 8.0 Hz, 1H), 6.94 (dd, J = 8.2, 1.6 Hz, 1H), 4.67 (s, 1H), 4.30-4.06 (m, 5H), 3.91(dd, J = 11.6,3.3 Hz, 1H), 3.83 (s, 3H), 3.74 (td, J = 11.7, 2.5 Hz, 1H), 3.58 (t, J = 10.3 Hz, 1H), 3.52 (d, J = 12.2 Hz, 1H), 3.37 (td, J = 12.0, 3.4Hz, 1H), 1.32 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.1 Hz, 3H).

[0217] 13 C NMR (101 MHz, CDCl3) δ 159.7, 155.3, 153.5,133.6, 129.4, 119.1,116.4, 111.2, 68.2, 66.2, 63.4, 63.3, 55.3, 54.6, 14.4, 14.1.

[0218] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 25 N4O6 + 393.1774; found 393.1759. Example 48

[0219] In this embodiment, 3-(m-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(m-tolyl)methylimine.

[0220] The target product weighed 56.4 mg, with a yield of 75% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 100-101 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 12.7 Hz, 2H), 7.26 (t, J = 7.6Hz, 1H), 7.20 (d, J = 7.5 Hz, 1H), 4.67 (d, J = 8.7 Hz, 1H), 4.26 (dddd, J =17.7, 10.6, 7.1, 3.5Hz, 3H), 4.19-4.13 (m, 1H), 4.09 (dt, J = 10.7, 7.1 Hz, 1H), 3.91 (dd, J = 11.6, 3.1Hz, 1H), 3.74 (td, J = 11.7, 2.5 Hz, 1H), 3.62-3.53 (m, 1H), 3.51 (d, J = 10.9 Hz, 1H), 3.36 (td, J = 12.0, 3.4 Hz, 1H), 2.37(s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.11 (t, J =7.1 Hz, 3H).

[0221] 13 C NMR (101 MHz, CDCl3) δ 155.4, 153.5, 150.3, 138.0,132.1, 130.9,128.3, 126.8, 123.8, 75.0, 68.2, 66.2, 63.3, 63.3, 54.6, 21.4, 14.4, 14.1.

[0222] HRMS (ESI) m / z: [M+H] + calcd for C 18 H 25 N4O5 + 377.1825; found 377.1806. Example 49

[0223] In this embodiment, 3-(3-bromophenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(3-bromophenyl)-N-morpholinylmethylimine.

[0224] The target product weighed 66.8 mg, with a yield of 76% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 102-103 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.50 (d, J= 8.7 Hz, 1H), 7.24 (t, J = 7.9 Hz, 1H), 4.76 (d, J = 7.8 Hz, 1H), 4.33-4.19 (m,3H), 4.16-4.05 (m, 2H), 3.90 (dd, J = 11.6, 3.2 Hz, 1H), 3.71 (td, J= 11.7, 2.5 Hz,1H), 3.57 (d, J = 10.3 Hz, 1H), 3.54-3.49 (m, 1H), 3.39 (td, J = 12.1, 3.4 Hz, 1H), 1.34 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.1 Hz, 3H).

[0225] 13 C NMR (101 MHz, CDCl3) δ 155.3, 153.2, 147.3, 134.5, 132.7, 129.9,129.3, 124.9, 122.5, 74.1, 67.8, 66.0,63.5, 63.5, 54.6, 14.4, 14.1.

[0226] HRMS (ESI) m / z: [M+H] + calcd for C 17 H 22 BrN4O5 + 441.0774; found 441.0752. Example 50

[0227] In this embodiment, 3-(3,5-dimethylphenyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(3,5-dimethylphenyl)-N-morpholinylmethylimine.

[0228] The target product weighed 54.7 mg, with a yield of 70% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 104-105 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 6.99 (s, 2H), 6.50 (t, J = 2.3 Hz, 1H), 4.65 (d, J = 9.6 Hz, 1H), 4.25 (dtd, J = 10.3, 7.1, 3.4 Hz, 3H), 4.20-4.07 (m,2H),3.91 (dd, J = 11.6, 3.2 Hz, 1H), 3.81 (s, 6H), 3.74 (td, J = 11.7, 2.5 Hz,1H), 3.58(t, J = 10.2 Hz, 1H), 3.51 (d, J = 13.4 Hz, 1H), 3.36 (td, J = 11.9,3.4Hz, 1H), 1.32 (t,J = 7.1 Hz, 3H), 1.14 (t,J = 7.1 Hz, 3H).

[0229] 13 C NMR (101 MHz, CDCl3) δ 160.8,155.3, 153.5, 150.1, 134.1, 104.4,102.8, 75.4, 68.3, 66.2, 63.4, 63.3, 55.5, 54.6, 14.4,14.2.

[0230] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 27 N4O5 + 391.1981; found 391.1973. Example 51

[0231] In this embodiment, 3-(thiophen-2-yl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(thiophen-2-yl)methylimine.

[0232] The target product weighed 54.5 mg, with a yield of 74% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 106-107 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.45 (s, 1H), 7.36 (d, J = 5.1 Hz, 1H), 7.06-6.97 (m,1H), 4.58 (d, J = 7.1 Hz, 1H), 4.33-4.11 (m, 5H), 3.92 (dd, J =11.6, 3.2 Hz, 1H), 3.74 (td, J = 11.7, 2.5 Hz, 1H), 3.62-3.54 (m, 1H), 3.45(d, J = 10.8 Hz, 1H), 3.31(td, J = 11.9, 3.4 Hz, 1H), 1.30 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H).

[0233] 13 C NMR (101 MHz, CDCl3) δ 155.3, 153.7, 135.4, 128.9, 128.3, 127.4,76.1, 68.7, 66.4,63.5, 63.2, 54.5, 29.7, 14.4, 14.1.

[0234] HRMS (ESI) m / z: [M+H] + calcd for C 15 H 21 N4O5S + 369.1233; found 369.1216. Example 52

[0235] In this embodiment, 3-(benzo[b]thiophene-3-yl)-6,7,9,9a-tetrahydro-[1,4]oxazin[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(benzo[b]thiophen-3-yl)-N-morpholinylmethylimine.

[0236] The target product weighed 61.8 mg, with a yield of 74% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 108-109 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 7.5 Hz, 1H), 7.99 (s, 1H), 7.85 (d, J = 6.2 Hz, 1H), 7.48-7.34 (m, 2H), 4.69 (s, 1H), 4.3 -4.16 (m, 4H), 4.15-4.05 (m, 1H), 3.96 (dd, J = 11.6, 3.3 Hz, 1H), 3.81 (td, J =11.7, 2.5Hz, 1H), 3.65 (t, J = 10.3 Hz, 1H), 3.59 (d, J = 10.9 Hz, 1H), 3.41 (td, J =12.0, 3.4 Hz, 1H), 1.33 (t, J = 7.1 Hz, 3H), 1.09 (t, J = 7.1 Hz, 3H).

[0237] 13 C NMR (101 MHz, CDCl3) δ 155.4, 153.9, 140.5, 135.6, 128.4, 125.0,125.0, 124.8,122.6, 75.3, 68.3, 66.3, 63.4, 63.3, 54.7, 14.5, 14.1.

[0238] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 23 N4O5S + 419.1389; found 419.1367. Example 53

[0239] In this embodiment, 3-(2,3-dihydrobenzofuran-5-yl)-6,7,9,9a-tetrahydro-[1,4]oxazinco[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-1-(2,3-dihydrobenzofuran-5-yl)-N-morpholinylmethylimine. The target product weighed 63.8 mg, with a yield of 79% and a purity ≥95%. The proton and carbon spectra are as follows: Figure 110-111 As shown, where: 1 H NMR (400 MHz, CDCl3) δ7.69 (s, 1H), 7.61 (d,J = 8.2 Hz, 1H), 6.76(d, J = 8.4 Hz, 1H), 4.60 (t, J = 8.7 Hz, 2H), 4.51 (s, 1H), 4.32-4.06 (m,5H), 3.91 (dd, J = 11.3, 2.8 Hz, 1H), 3.79-3.72 (m, 1H), 3.58 (t, J =10.2 Hz,1H), 3.45 (d, J = 10.8 Hz, 1H), 3.30 (td, J = 11.8, 3.3 Hz, 1H), 3.21 (t, J =8.7 Hz, 2H), 1.30 (t, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H).

[0240] 13 C NMR (101 MHz, CDCl3) δ 162.2, 155.4, 153.7, 127.5, 127.5, 124.6,123.2, 109.2, 76.1, 71.8,68.6, 66.4, 63.3, 63.2, 54.6, 29.3, 14.4, 14.2.

[0241] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 25 N4O6 +405.1774; found 405.1755. Example 54

[0242] In this embodiment, 3-(naphthyl-2-yl)-6,7,9,9a-tetrahydro-[1,4]oxazinco[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-morpholino-1-(naphth-2-yl)methylimine.

[0243] The target product weighed 63.4 mg, with a yield of 77% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 112-113 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 8.28 (s, 1H), 7.94 (d, J = 8.7Hz, 1H), 7.89-7.79 (m, 3H), 7.54-7.45 (m, 2H), 4.71 (d, J = 9.6 Hz, 1H), 4.3-4.17 (m, 4H),4.15-4.06 (m, 1H), 3.95 (dd, J = 11.5, 3.3 Hz, 1H), 3.79 (td, J =11.7, 2.5Hz, 1H), 3.64 (t, J = 10.3 Hz, 1H), 3.57 (d, J = 10.9 Hz, 1H), 3.41 (td, J =11.9, 3.4 Hz, 1H), 1.36 (t, J = 7.1 Hz, 3H), 1.07 (t, J = 7.1 Hz, 3H).

[0244] 13 C NMR (101 MHz, CDCl3) δ 155.4, 153.7, 150.5, 134.2, 133.0, 129.5,128.7, 128.2,127.8, 127.0, 126.9, 126.5, 123.1, 75.3, 68.4, 66.3, 63.4, 63.3,54.7, 14.5, 14.1.

[0245] HRMS (ESI) m / z: [M+H] +calcd for C 21 H 25 N4O5 + 413.1825; found 413.1805. Example 55

[0246] In this embodiment, 3-(p-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-hexacyclic-1,2-dicarboxylic acid diisopropyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that diethyl azodicarboxylate is replaced with an equimolar amount of diisopropyl azodicarboxylate.

[0247] The target product weighed 55.8 mg, with a yield of 69% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 114-115 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.7 Hz, 2H), 7.17 (d, J = 8.0Hz, 2H), 5.00 (p, J = 6.2 Hz, 1H), 4.91 (h, J = 6.2 Hz, 1H), 4.68 (s, 1H), 4.14 (dd, J = 10.8, 3.3 Hz, 1H), 3.89 (dd, J = 11.6, 3.2 Hz, 1H), 3.72 (td, J= 11.6, 2.5 Hz, 1H), 3.56 (t, J= 10.3 Hz, 1H), 3.49 (d, J = 12.2 Hz, 1H),3.35 (td, J = 12.0, 3.4 Hz, 1H), 2.36 (s, 3H), 1.32 (d, J = 6.2 Hz, 3H), 1.28 (d, J = 6.3 Hz, 3H), 1.17 (d, J = 6.2 Hz, 3H), 1.10 (d, J= 6.2 Hz, 3H).

[0248] 13 C NMR (101 MHz, CDCl3) δ 154.9, 152.9, 140.2, 129.7, 129.0, 126.4, 71.3, 71.2, 68.1, 66.1, 54.5, 22.0, 22.0, 21.7, 21.5, 21.5.

[0249] HRMS (ESI) m / z: [M+H] + calcd for C 20 H 29 N4O5 + 405.2138; found 405.2121. Example 56

[0250] In this embodiment, 3-(p-tolyl)-6,7,9,9a-tetrahydro-[1,4]oxazino[4,3-b][1,2,4,5]tetraaza-6-membered heterocyclic-1,2-dicarboxylic acid dibenzyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as in Example 31, except that diethyl azodicarboxylate is replaced with an equimolar amount of dibenzyl azodicarboxylate.

[0251] The target product weighed 65.0 mg, with a yield of 65% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 116-117 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.62 (s, 2H), 7.32 (dp, J = 10.2, 3.5, 3.0Hz, 5H), 7.26-7.18 (m, 3H), 7.08 (d, J = 7.3 Hz, 2H), 7.01 (d, J = 6.6 Hz,2H), 5.26-4.99 (m, 4H),4.64 (d, J = 9.6 Hz, 1H), 4.13 (d, J = 11.3 Hz, 1H), 3.86 (d, J = 11.6Hz, 1H), 3.65 (td,J = 11.7, 2.5 Hz, 1H), 3.54-3.47 (m, 1H),3.44 (d, J = 13.2 Hz, 1H), 3.31 (td, J =11.9, 3.3 Hz, 1H), 2.35 (s, 3H).

[0252] 13C NMR (101 MHz, CDCl3) δ155.2, 153.5,150.8, 140.5, 135.1, 129.2,129.1, 128.7, 128.6, 128.4, 128.3, 128.2, 127.6, 126.5,75.4, 68.9, 68.6,68.3, 66.2, 54.5, 21.5.

[0253] HRMS (ESI) m / z: [M+H] + calcd for C 28 H 29 N4O5 + 501.2138; found 501.2127. Example 57

[0254] In this embodiment, 3-(p-tolyl)-7,8,9,9a-tetrahydro-2H-pyrido[1,2-b][1,2,4,5]tetranitrogen six-membered heterocyclic-1,2(6H)-dicarboxylic acid diethyl ester was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholin-4-amine is replaced with an equimolar amount of (E)-N-(piperidin-1-yl)-1-(p-tolyl)methylimine.

[0255] The target product weighed 53.1 mg, with a yield of 71% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 118-119 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 7.8 Hz, 2H), 7.15 (d, J =7.9Hz, 2H), 4.82 (s, 1H), 4.30-4.15 (m, 3H), 4.13-4.03 (m, 1H), 3.68 (dd, J =12.0, 2.3 Hz, 1H), 3.15-3.05 (m, 1H), 2.35 (s, 3H), 2.02 (d, J = 12.5 Hz,1H), 1.88(d, J = 15.3 Hz, 1H), 1.73 (dd, J = 11.5, 3.9 Hz, 1H), 1.57-1.46 (m,1H), 1.32 (t, J = 7.1 Hz, 3H), 1.10 (t, J = 7.1 Hz, 3H).

[0256] 13 C NMR (101 MHz, CDCl3) δ 155.6, 153.7, 139.1, 130.7, 128.9, 126.1, 63.0, 63.0, 55.8, 55.2, 25.6, 23.9, 23.3, 21.4, 14.5, 14.1.

[0257] HRMS (ESI) m / z: [M+H] + calcd for C 19 H 27 N4O4 + 375.2032; found370.2021. Example 58

[0258] In this embodiment, diethyl 4-benzyl-3-phenyl-6-(p-tolyl)-3,4-dihydro-1,2,4,5-tetraaza-hexacyclic-1,2-dicarboxylic acid was synthesized, with the following structural formula: ; The specific preparation steps in this embodiment are exactly the same as those in Example 31, except that (E)-N-(4-methylmethylene)morpholine-4-amine is replaced with an equimolar amount of (E)-1-(4-methylbenzyl)-2-phenylhydrazine.

[0259] The target product weighed 31.1 mg, with a yield of 32% and a purity ≥95%. The proton and carbon spectra are as follows: Figures 120-121 As shown, where: 1 H NMR (400 MHz, CDCl3) δ 7.53 (s, 2H), 7.35 (d, J = 6.3 Hz, 2H), 7.33-7.21 (m,8H), 7.16 (d, J = 7.9 Hz, 2H), 6.49 (s, 1H), 4.54 (s, 2H), 4.28-4.03 (m, 2H), 3.66 (dq, J = 10.5, 7.1 Hz, 1H), 3.51 (s, 1H), 2.34 (s, 3H), 1.35-1.09 (m, 3H), 0.72 (t, J= 7.2 Hz, 3H).

[0260] 13C NMR (101 MHz, CDCl3) δ 155.2, 152.4, 138.2, 136.8,136.3, 135.2,131.8, 128.9, 128.8, 128.6, 128.4, 128.3, 127.8, 127.7, 125.8, 74.3, 63.5,62.5, 21.4, 14.4, 13.7。

[0261] HRMS (ESI) m / z:[M+H] + calcd for C 28 H 31 N4O4 + 487.2345;found 487.2335。

Claims

1. An N-aminohydrazone derivative, characterized in that: Its general structural formulas are Formula I and Formula II, where Formula I is... Formula II is Wherein, Ar- is phenyl, substituted phenyl, aryl, or heteroaryl; the substituted phenyl is a phenyl substituted with one or more substituents selected from methyl, ethyl, tert-butyl, methoxy, dimethylamino, phenyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, and cyano; the aryl is biphenyl-4-yl, naphthio-2-yl, or 2,3-dihydrobenzofuran-5-yl; the heteroaryl is pyridin-2-yl, thiophene-2-yl, or benzo[b]thiophene-3-yl; R'' represents ethyl, isopropyl, tert-butyl, or benzyl. In Formula I, the two R's together constitute a morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative; In Formula II, R' is morpholino, piperidin-1-yl, or 2-phenylhydrazine derivative, and R''' is H or phenyl. When R' is morpholino or piperidin-1-yl, R''' is H; when R' is 2-phenylhydrazine derivative, R''' is phenyl.

2. A method for preparing the N-aminohydrazone derivative according to claim 1, characterized in that, The specific steps for preparing Formula I are as follows: using aldehyde hydrazone compounds and azodicarboxylic acid ester compounds as reactants, adding solvent and heating the reaction, and after the reaction is completed, post-treatment is performed to obtain the target product Formula I.

3. The method for preparing the N-aminohydrazone derivative according to claim 2, characterized in that: The aldehyde hydrazone compound is one of the following substances: (E)-N-morpholino-1-(p-tolyl)methylimine, (E)-N-morpholino-1-phenylmethylimine, (E)-1-(4-methoxyphenyl)-N-morpholinomethylimine, (E)-N,N-dimethyl-4-((morpholinoimino)methyl)aniline, (E)-1-(4-ethylphenyl)-N-morpholinomethylimine, (E)-1-(4-tert-butylphenyl)-N-morpholinomethylimine, (E)-1-([1 [1'-Biphenyl]-4-yl)-N-morpholinylmethylimine, (E)-1-(4-fluorophenyl)-N-morpholinylmethylimine, (E)-1-(4-chlorophenyl)-N-morpholinylmethylimine, (E)-1-(4-bromophenyl)-N-morpholinylmethylimine, (E)-1-(4-iodophenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(4-trifluoromethylphenyl)methylimine, (E)-N-morpholinyl-1-(4-nitrophenyl)methylimine, (E)-4- ((morpholinylimino)methyl)benzonitrile, (E)-1-(2-methoxyphenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(o-tolyl)methylimine, (E)-1-(3-methoxyphenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(m-tolyl)methylimine, (E)-1-(3-bromophenyl)-N-morpholinylmethylimine, (E)-1-(3,5-dimethylphenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl- 1-(pyridin-2-yl)methylimine, (E)-N-morpholino-1-(thiophen-2-yl)methylimine, (E)-1-(benzo[b]thiophen-3-yl)-N-morpholinomethylimine, (E)-1-(2,3-dihydrobenzofuran-5-yl)-N-morpholinomethylimine, (E)-N-morpholino-1-(naphth-2-yl)methylimine, (E)-N-(piperidin-1-yl)-1-(p-tolyl)methylimine, (E)-1-(4-methylbenzylene)-2-phenylhydrazine.

4. The method for preparing the N-aminohydrazone derivative according to claim 2, characterized in that: The solvent is acetonitrile, and the molar ratio of aldehyde hydrazone to azodicarboxylic acid ester is 1:2; the molar ratio of aldehyde hydrazone to solvent is 1 mol: 10~20 L; the reaction temperature is 55℃.

5. A method for preparing the N-aminohydrazone derivative according to claim 1, characterized in that: The specific steps for preparing Formula II are as follows: using a "one-pot two-step" method, aldehyde hydrazone compounds and azodicarboxylic acid ester compounds are used as raw materials, solvent is added and heated to react, after the reaction, a photocatalyst and a metal catalyst are added to the reaction system, and further oxidation is carried out under blue light irradiation. After the reaction is completed, the target product Formula II is obtained through post-treatment.

6. The method for preparing the N-aminohydrazone derivative according to claim 5, characterized in that: The aldehyde hydrazone compound is one of the following substances: (E)-N-(4-methylmethylene)morpholin-4-amine, (E)-N-morpholinyl-1-(p-tolyl)methylimine, (E)-1-(4-methoxyphenyl)-N-morpholinylmethylimine, (E)-1-(4-ethylphenyl)-N-morpholinylmethylimine, (E)-1-(4-tert-butylphenyl)-N-morpholinylmethylimine, (E)-1-([1,1'-biphenyl]-4-yl)-N-morpholinyl Methylimine, (E)-1-(4-fluorophenyl)-N-morpholinylmethylimine, (E)-1-(4-chlorophenyl)-N-morpholinylmethylimine, (E)-1-(4-bromophenyl)-N-morpholinylmethylimine, (E)-1-(4-iodophenyl)-N-morpholinylmethylimine, (E)-N-morpholinyl-1-(4-trifluoromethylphenyl)methylimine, (E)-N-morpholinyl-1-(4-nitrophenyl)methylimine, (E)-4-((morpholinylimine)methyl) Benzonitrile, (E)-1-(2-methoxyphenyl)-N-morpholinyl methylimine, (E)-N-morpholinyl-1-(o-tolyl) methylimine, (E)-1-(2-fluorophenyl)-N-morpholinyl methylimine, (E)-1-(3-methoxyphenyl)-N-morpholinyl methylimine, (E)-N-morpholinyl-1-(m-tolyl) methylimine, (E)-1-(3-bromophenyl)-N-morpholinyl methylimine, (E)-1-(3,5-dimethylphenyl)-N- Morpholinyl methylimine, (E)-N-morpholinyl-1-(thiophen-2-yl)methylimine, (E)-1-(benzo[b]thiophen-3-yl)-N-morpholinyl methylimine, (E)-1-(2,3-dihydrobenzofuran-5-yl)-N-morpholinyl methylimine, (E)-N-morpholinyl-1-(naphth-2-yl)methylimine, (E)-N-(piperidin-1-yl)-1-(p-tolyl)methylimine, (E)-1-(4-methylbenzylene)-2-phenylhydrazine.

7. The method for preparing the N-aminohydrazone derivative according to claim 5, characterized in that: The photocatalyst is 9-trimethyl-10-methylacridinium tetrafluoroborate, and the metal catalyst is nickel acetate tetrahydrate.

8. The method for preparing the N-aminohydrazone derivative according to claim 5, characterized in that: Using aldehyde hydrazones and azodicarboxylic acid esters in a molar ratio of 1:2 as raw materials, acetonitrile was added as solvent and the mixture was heated to 55°C. The molar volume ratio of aldehyde hydrazones to solvent was 1 mol: 10~20 L. After the reaction, a photocatalyst and a metal catalyst were added to the reaction system, and the mixture was further oxidized under blue light irradiation. The oxidant was oxygen. The molar amount of the photocatalyst was 2 mol% of the aldehyde hydrazones, and the molar amount of the metal catalyst was 5 mol% of the aldehyde hydrazones.

9. The method for preparing the N-aminohydrazone derivative according to claim 2 or 5, characterized in that: The azodicarboxylic acid ester compound is one of the following substances: diethyl azodicarboxylate, diisopropyl azodicarboxylate, ditert-butyl azodicarboxylate, or dibenzyl azodicarboxylate.

10. The method for preparing the N-aminohydrazone derivative according to claim 2 or 5, characterized in that: After the reaction was completed, the reaction system was first quenched with water, then extracted with dichloromethane, and then dried with anhydrous sodium sulfate, purified by vacuum distillation and column chromatography.

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