Industrial preparation method of 4-(6-aminopyridine-3-yl) piperazine-1-carboxylic acid tert-butyl ester
By conducting a coupling reaction under copper catalyst, alkali and solvent conditions, 2-amino-5-halopyridine and 1-Boc-piperazine are directly converted into tert-butyl 4-(6-aminopyridine-3-yl)piperazine-1-carboxylic acid tert-butyl ester in the prior art, the problem of high raw materials and production costs is solved, and a high-efficiency and low-cost preparation method is achieved.
Patent Information
- Application Number
- CN202311298230.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-10-09
- Publication Date
- 2025-04-18
AI Technical Summary
In the existing synthesis methods of tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid tert, the raw materials and production costs are high, and the oxygen content is strictly controlled, resulting in complex production and high cost.
The coupling reaction of 2-amino-5-halopyridine and 1-Boc-piperazine under copper catalyst, base and solvent conditions was carried out to prepare tert-butyl 4-(6-aminopyridine-3-yl)piperazine-1-carboxylic acid. The process has short steps, cheap raw materials, high catalyst efficiency, and no need to control the oxygen content.
The efficient preparation of tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid is achieved, which reduces production costs, simplifies the process flow, and is suitable for industrial production.
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Abstract
Description
Technical Field
[0001] The invention relates to the field of pharmaceutical intermediate preparation, and in particular to an industrial preparation method of tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate. Background Art
[0002] Tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate is one of the key intermediates for the synthesis of palbociclib and ribociclib. Palbociclib is a breakthrough breast cancer drug developed by Pfizer. It was approved by the FDA for marketing in the United States in 2015 and in China in 2018. Ribociclib is a highly specific dual inhibitor of cell cycle-dependent kinase CDK4 / 6 developed by Novartis for the treatment of advanced or metastatic breast cancer. It was approved for marketing by the US FDA in March 2017. Palbociclib and ribociclib are first-line drugs for the treatment of breast cancer, with a broad market and important value.
[0003]
[0004] The currently reported method for synthesizing tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate is mainly to start from 2-halogenated-5-nitropyridine, undergo a substitution reaction or a metal-catalyzed coupling reaction with 1-N-Boc-piperazine, and then reduce the nitro group to obtain it. The raw material 2-halogenated-5-nitropyridine used in this method is difficult to prepare, has a high level of three wastes, and involves dangerous oxidation reactions, resulting in high costs.
[0005]
[0006] Another method is to start from 2-halogenated-5-aminopyridine. For example, patent CN113429340 and document [RSCAdvances, 2017, 7, 44366–44370] reported the coupling reaction of 2-iodo-5-aminopyridine and 1-Boc-piperazine to obtain 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester in one step. This method uses 2-iodo-5-aminopyridine as a raw material, as well as expensive palladium catalysts and ligands, and needs to control the oxygen content of the reactor to no more than 0.4%, resulting in high overall production costs.
[0007]
[0008] In summary, the current synthesis method of tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate has high raw material and production costs, and there is still much room for improvement.
[0009] Therefore, it is necessary to develop a method for preparing tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate with short steps, cheap raw materials, low catalyst cost and high efficiency, great cost advantage, no need to control strict reaction conditions such as oxygen content, simple reaction operation, easy industrial production and high yield. Summary of the invention
[0010] The purpose of the present invention is to provide a method for preparing tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate, which has the advantages of cheap raw materials, simple preparation method, high catalyst efficiency, low cost and easy industrial production.
[0011] In a first aspect of the present invention, there is provided a method for preparing tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate (Formula III), the method comprising the steps of:
[0012] In the presence of a solvent, 2-amino-5-halopyridine (Formula I) and 1-Boc-piperazine (Formula II) undergo a coupling reaction under catalyst and base conditions to obtain 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester (Formula III).
[0013]
[0014] Wherein, X is a halogen.
[0015] In another preferred embodiment, X is Cl, Br or I, preferably Br.
[0016] In another preferred embodiment, the catalyst is a combination of a copper salt and a ligand.
[0017] In another preferred embodiment, the copper salt is selected from Cu powder, CuI, CuBr, CuCl, CuTc, CuCN, CuSCN, Cu2O, Cu(OAc)2, CuSO4, Cu2CO3, Cu(NO3)2, CuBr2, CuCl2, CuO, Cu(acac)2, 8-hydroxyquinoline copper, or a combination thereof.
[0018] In another preferred embodiment, the copper salt is Cu2O or CuBr.
[0019] In another preferred embodiment, the ligand has a structure of any one of the following formulas a to e:
[0020]
[0021] In the formula,
[0022] R a , R b , R c , R d and Re Each is independently H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C10 aryl;
[0023] Rf is H, hydroxyl, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, or substituted or unsubstituted C6-C10 aryl;
[0024] Rg is H or a substituted or unsubstituted C1-C6 alkyl group.
[0025] Among them, any "substitution" mentioned means that 1 to 4 hydrogen atoms on the group are independently replaced by substituents selected from the following group: C1-C6 alkyl, C1-C6 alkoxy, halogen, nitro, cyano, hydroxyl, amino, C1-C4 carboxyl, C2-C4 ester, C2-C4 amide, C1-C6 haloalkoxy, C6-C10 aryl, 5-8 membered heteroaryl.
[0026] In another preferred embodiment, R a , R b , R c , R d and R e Each is independently a substituted or unsubstituted C1-C4 alkyl group, or a substituted or unsubstituted C6-C10 aryl group.
[0027] In another preferred embodiment, any "substitution" mentioned above means that 1 to 4 hydrogen atoms on the group are independently replaced by substituents selected from the following group: C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxyl, amino, C6-C10 aryl, 5-8 membered heteroaryl.
[0028] In another preferred embodiment, the ligand has a structure shown in formula a, wherein R a , R b Each is independently a substituted or unsubstituted C6-C10 aryl group, or a substituted or unsubstituted C1-C4 alkyl group, wherein any "substitution" mentioned means that 1 to 4 hydrogen atoms on the group are independently replaced by a substituent selected from the following group: C1-C6 alkyl group, C1-C6 alkoxy group, and 5-8 membered heteroaryl group.
[0029] In another preferred embodiment, the ligand has a structure shown in formula a, wherein R a , R b Each is independently a C6-C10 aryl group substituted by a C1-C6 alkyl group, or a C1-C6 alkyl group substituted by a 5-8 membered heteroaryl group.
[0030] In another preferred embodiment, the ligand is selected from N1, N2-bis (2-methyl-1-naphthyl) oxalamide, N1- (2-furylmethyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1- (2-pyridylmethyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1- (2-benzyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1- (2-thienylmethyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1, N2-bis (2,4,6-trimethoxyphenyl) oxalamide, N1 , N2-bis(2,4-dimethoxyphenylmethyl)oxalamide, N1,N2-bis(2,3,4-trimethoxyphenylmethyl)oxalamide, N1-(2-phenylphenyl)-N2-benzyloxalamide, N1,N2-bis(2-phenylethyl)oxalamide, N1-(2,6-dimethylphenyl)-N2-(phenylmethyl)oxalamide, N1-(2,4,6-trimethoxyphenyl)-N2-(phenylmethyl)oxalamide, N1,N2-bisphenyloxalamide, N1-(9-aminoanthracene)-N2-(2-methylpyridine oxamide, N1,N2-bis(furan-2-ylmethyl)oxamide, N1,N2-bis(2-thienylmethyl)-oxalamide, N1,N2-bis(4-hydroxy-2,6-dimethylphenyl)oxalamide, N1,N2-bis(4-hydroxy-2,6-diethylphenyl)oxalamide, N1-(4-hydroxy-2,6-diethylphenyl)-N2-(pyridin-2-ylmethyl)oxalamide, N1-(4-hydroxy-2,6-dimethylphenyl)-N2-(2-furanmethyl)oxalamide, N1-(2,6- N-(2,6-dimethylphenyl)-N2-(pyridin-2-ylmethyl)oxalamide, N1,N2-bis(1-naphthylmethyl)-oxalamide, N1-(2-methyl-1-naphthyl)-N2-(phenylmethyl)-oxalamide, N-(2,6-diethylphenyl)picolinamide, N-(2,6-dimethylphenyl)-6-hydroxypicolinamide, N-(2,6-dimethylphenyl)-4-hydroxypicolinamide, N-(2,6-dimethylphenyl)-5-hydroxypicolinamide, 8-hydroxyquinoline, 1,10-phenanthroline, or a combination thereof.
[0031] In another preferred embodiment, the ligand is selected from one of N1,N2-bis(2-methyl-1-naphthyl)oxalamide, N1-(2-furanmethyl)-N2-(2-methyl-1-naphthyl)oxalamide or a combination thereof.
[0032] In another preferred embodiment, the base is one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, triethylamine, tripropylamine, diisopropylethylamine, DBU, DABCO, pyridine, 2-methylpyridine, 2,6-lutidine, and tetrabutylammonium hydroxide.
[0033] In another preferred embodiment, the solvent includes one or more of water, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), sulfolane, toluene, acetonitrile, alcohol solvents, ether solvents, ketone solvents, and ester solvents.
[0034] In another preferred embodiment, the amount of the copper salt is 0.001-0.5wt% of the compound of formula I, preferably 0.001-0.002wt%, such as 0.002wt%, 0.004wt%, 0.017wt%.
[0035] In another preferred embodiment, the amount of the ligand is 0.001-0.5wt% of the compound of formula I, preferably 0.001-0.1wt%, such as 0.004wt%, 0.0085wt%, 0.0105wt%, 0.042wt%.
[0036] In another preferred embodiment, the mass ratio of the copper salt to the ligand is 1:1 to 1:20, preferably 1:1 to 1:5.
[0037] In another preferred example, the mass ratio of the base to the compound of formula I is 5:1 to 1:5, preferably 2:1 to 1:2.
[0038] In another preferred embodiment, the volume mass ratio of the solvent to the volume mass ratio of the compound of formula I is 2-20 ml / g, preferably 4-10 ml / g, for example 5 ml / g.
[0039] In another preferred embodiment, the reaction temperature of the coupling reaction is 60-180°C, preferably 80-130°C.
[0040] In another preferred embodiment, the reaction time of the coupling reaction is 2-24 hours, preferably 8-10 hours.
[0041] In another preferred embodiment, the method comprises: adding a compound of formula I, a compound of formula II, a base, a copper salt and a ligand into a reaction container, heating to a reaction temperature, and performing post-treatment after a period of reaction to obtain the tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate.
[0042] In another preferred embodiment, the method further comprises a post-processing step.
[0043] In another preferred embodiment, the post-treatment step includes: cooling, filtering, adding water to the filtrate and stirring, then filtering, rinsing with water, and drying.
[0044] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as embodiments) can be combined with each other to form a new or preferred technical solution. Due to space limitations, they will not be described one by one here. DETAILED DESCRIPTION
[0045] After extensive and in-depth research, the inventors have discovered for the first time a method for preparing tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate by direct coupling of 2-amino-5-halopyridine and 1-Boc-piperazine under the action of a copper catalyst. The method has short steps, cheap raw materials, low catalyst cost and high efficiency, has a large cost advantage, does not require strict reaction conditions such as controlling oxygen content, is simple in reaction operation, is easy to industrialize and produce, and has a high yield. The present invention was completed on this basis.
[0046] the term
[0047] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
[0048] As used herein, the terms "comprise", "include", and "contain" are used interchangeably and include not only closed definitions, but also semi-closed and open definitions. In other words, the terms include "consisting of", "consisting essentially of".
[0049] As used herein, when used in reference to a specific recited numerical value, the term "about" means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes all values between 99 and 101 (e.g., 99.1, 99.2, 99.3, 99.4, etc.).
[0050] Preparation method of tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate
[0051] The present invention provides a method for preparing tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate, which is achieved by the following technical route:
[0052]
[0053] X = Cl, Br or I, preferably Br.
[0054] The preparation method of 4-(6-aminopyridine-3-yl)piperazine-1-carboxylic acid tert-butyl ester of the present invention involves a coupling reaction between 2-amino-5-halopyridine and 1-Boc-piperazine under the conditions of a copper catalyst / base / solvent to prepare 4-(6-aminopyridine-3-yl)piperazine-1-carboxylic acid tert-butyl ester.
[0055] The catalyst consists of copper salt and ligand.
[0056] The copper salt is selected from Cu powder, CuI, CuBr, CuCl, CuTc, CuCN, CuSCN, Cu2O, Cu(OAc)2, CuSO4, Cu2CO3, Cu(NO3)2, CuBr2, CuCl2, CuO, Cu(acac)2, 8-hydroxyquinoline copper or a combination thereof; Cu2O and CuBr are preferred.
[0057] The ligand in the reaction has the structure shown below:
[0058]
[0059] In the formula,
[0060] Ra, Rb, Rc, Rd and Re are each independently H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C10 aryl;
[0061] Rf is H, hydroxyl, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, or substituted or unsubstituted C6-C10 aryl;
[0062] Rg is H or a substituted or unsubstituted C1-C6 alkyl group;
[0063] Among them, any "substitution" mentioned means that 1 to 4 hydrogen atoms on the group are independently replaced by substituents selected from the following group: C1-C6 alkyl, C1-C6 alkoxy, halogen, nitro, cyano, hydroxyl, amino, C1-C4 carboxyl, C2-C4 ester, C2-C4 amide, C1-C6 haloalkoxy, C6-C10 aryl, 5-8 membered heteroaryl.
[0064] The ligand is selected from N1,N2-bis(2-methyl-1-naphthyl)oxalamide, N1-(2-furylmethyl)-N2-(2-methyl-1-naphthyl)oxalamide, N1-(2-pyridylmethyl)-N2-(2-methyl-1-naphthyl)oxalamide, N1-(2-benzyl)-N2-(2-methyl-1-naphthyl)oxalamide, N1-(2-thienylmethyl)-N2-(2-methyl-1-naphthyl)oxalamide, N1,N2-bis(2,4,6-trimethoxyphenyl)oxalamide, N1,N2-bis(2, 4-dimethoxyphenylmethyl)oxalamide, N1,N2-bis(2,3,4-trimethoxyphenylmethyl)oxalamide, N1-(2-phenylphenyl)-N2-benzyloxalamide, N1,N2-bis(2-phenylethyl)oxalamide, N1-(2,6-dimethylphenyl)-N2-(phenylmethyl)oxalamide, N1-(2,4,6-trimethoxyphenyl)-N2-(phenylmethyl)oxalamide, N1,N2-bisphenyloxalamide, N1-(9-aminoanthracene)-N2-(2-methylpyridine)oxalamide, N1,N2-bis(furan-2-ylmethyl)oxalamide, N1,N2-bis(2-thienylmethyl)-oxalamide, N1,N2-bis(4-hydroxy-2,6-dimethylphenyl)oxalamide, N1,N2-bis(4-hydroxy-2,6-diethylphenyl)oxalamide, N1-(4-hydroxy-2,6-diethylphenyl)-N2-(pyridin-2-ylmethyl)oxalamide, N1-(4-hydroxy-2,6-dimethylphenyl)-N2-(2-furanmethyl)oxalamide, N1-(2,6-dimethylphenyl)- One or more of N-(2,6-diethylphenyl)-pyridineamide, N-(2,6-dimethylphenyl)-6-hydroxypyridineamide, N-(2,6-dimethylphenyl)-4-hydroxypyridineamide, N-(2,6-dimethylphenyl)-5-hydroxypyridineamide, 8-hydroxyquinoline, and 1,10-phenanthroline.
[0065] Among them, the better ligand is one of N1,N2-bis(2-methyl-1-naphthyl)oxalyl, N1-(2-furanmethyl)-N2-(2-methyl-1-naphthyl)oxalamide or a combination thereof.
[0066] The base is one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, triethylamine, tripropylamine, diisopropylethylamine, DBU, DABCO, pyridine, 2-methylpyridine, 2,6-lutidine, and tetrabutylammonium hydroxide, among which potassium carbonate and potassium phosphate are preferred.
[0067] The solvent includes one or more of water, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), sulfolane, toluene, acetonitrile, alcohol solvents, ether solvents, ketone solvents, and ester solvents, among which DMF and DMAc are preferred.
[0068] The amount of the copper salt is 0.1-20 mol%, preferably 0.1-5 mol%, or 0.002 mol%, or 0.005 mol%, or 0.021 mol% of the compound of formula I.
[0069] The amount of the ligand is 0.1-20 mol%, preferably 0.1-5 mol%, or 0.002 mol%, or 0.005 mol%, or 0.020 mol% of the compound of formula I.
[0070] The mass ratio of the copper salt to the ligand is 1:1 to 1:20, preferably 1:1 to 1:5.
[0071] The equivalent of the base is 1 to 20 times the molar equivalent of the compound of formula I, for example, 2 times the equivalent.
[0072] The volume of the solvent for the coupling reaction is 1 to 20 times, for example 5 times, the volume of the compound of formula I.
[0073] The reaction temperature of the coupling reaction is 60-180°C, preferably 80-130°C.
[0074] The reaction time of the coupling reaction is 2-24 hours, preferably 8-10 hours.
[0075] The main advantages of the present invention include:
[0076] The method of the invention directly couples 2-amino-5-halopyridine and 1-Boc-piperazine under the action of a copper catalyst to obtain 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester. The method has short steps, cheap raw materials, high catalyst efficiency and great cost advantage.
[0077] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples without specifying specific conditions are usually based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.
[0078] Example 1
[0079] Add 200g of 2-amino-5-bromopyridine and 280g of 1-Boc-piperazine, 1000ml of DMF, 0.8g of CuBr, 2.1g of N1, N2-bis(2-methyl-1-naphthyl)oxalamide, and 319g of potassium carbonate to the reaction bottle, heat to 80-100°C, react for 10h, and the reaction is complete. Cool to 20-30°C, filter, add 1500g of water to the filtrate, stir for 2h. Filter, rinse with water, and dry to obtain 274g of the product with a yield of 85%.
[0080] Example 2
[0081] Add 200g of 2-amino-5-chloropyridine and 280g of 1-Boc-piperazine, 1000ml of DMSO, 3.4g of CuBr, 8.4g of N1, N2-bis(2-methyl-1-naphthyl)oxalamide, and 319g of potassium carbonate to the reaction bottle, heat to 120-130°C, react for 16h, and the reaction is complete. Cool to 20-30°C, filter, add 1500g of water to the filtrate, and stir for 2h. Filter, rinse with water, and dry to obtain 241g of the product with a yield of 75%.
[0082] Example 3
[0083] Add 200g of 2-amino-5-bromopyridine and 280g of 1-Boc-piperazine, 1000ml of DMF, 0.8g of CuBr, 1.7g of N1-(2-furanylmethyl)-N2-(2-methyl-1-naphthyl)oxalamide, and 319g of potassium carbonate to the reaction bottle, heat to 80-100°C, react for 10h, and the reaction is complete. Cool to 20-30°C, filter, add 1500g of water to the filtrate, and stir for 2h. Filter, rinse with water, and dry to obtain 283g of the product with a yield of 88%.
[0084] Example 4
[0085] Add 200g of 2-amino-5-bromopyridine and 280g of 1-Boc-piperazine, 1000ml of DMF, 0.4g of CuBr, 0.8g of N1-(2-furanylmethyl)-N2-(2-methyl-1-naphthyl)oxamide, and 319g of potassium carbonate to the reaction bottle, heat to 80-100°C, react for 10h, and the reaction is complete. Cool to 20-30°C, filter, add 1500g of water to the filtrate, and stir for 2h. Filter, rinse with water, and dry to obtain 260g of product with a yield of 81%.
[0086] All documents mentioned in the present invention are cited as references in this application, just as each document is cited as reference individually. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.
Claims
1. A method for preparing tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate, characterized in that: The method comprises the steps of: In the presence of a solvent, 2-amino-5-halopyridine (Formula I) and 1-Boc-piperazine (Formula II) undergo a coupling reaction under catalyst and base conditions to obtain 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester (Formula III). Wherein, X is a halogen; The catalyst is a combination of a copper salt and a ligand.
2. The preparation method according to claim 1, characterized in that The copper salt is selected from Cu powder, CuI, CuBr, CuCl, CuTc, CuCN, CuSCN, Cu2O, Cu(OAc)2, CuSO4, Cu2CO3, Cu(NO3)2, CuBr2, CuCl2, CuO, Cu(acac)2, 8-hydroxyquinoline copper, or a combination thereof; The ligand has a structure of any one of the following formulas a to e: In the formula, R a , R b , R c , R d and R e Each is independently H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C10 aryl; Rf is H, hydroxyl, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, or substituted or unsubstituted C6-C10 aryl; Rg is H or a substituted or unsubstituted C1-C6 alkyl group; Wherein, any "substitution" mentioned means that 1 to 4 hydrogen atoms on the group are independently replaced by substituents selected from the following group: C1-C6 alkyl, C1-C6 alkoxy, halogen, nitro, cyano, hydroxyl, amino, C1-C4 carboxyl, C2-C4 ester, C2-C4 amide, C1-C6 haloalkoxy, C6-C10 aryl, 5-8 membered heteroaryl.
3. The preparation method according to claim 1, characterized in that: The ligand is selected from N1, N2-bis (2-methyl-1-naphthyl) oxalamide, N1- (2-furylmethyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1- (2-pyridylmethyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1- (2-benzyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1- (2-thienylmethyl) -N2- (2-methyl-1-naphthyl) oxalamide, N1, N2-bis (2,4,6-trimethoxyphenyl) oxalamide, N1, N2-bis ( 2,4-dimethoxyphenylmethyl)oxalamide, N1,N2-bis(2,3,4-trimethoxyphenylmethyl)oxalamide, N1-(2-phenylphenyl)-N2-benzyloxalamide, N1,N2-bis(2-phenylethyl)oxalamide, N1-(2,6-dimethylphenyl)-N2-(phenylmethyl)oxalamide, N1-(2,4,6-trimethoxyphenyl)-N2-(phenylmethyl)oxalamide, N1,N2-bisphenyloxalamide, N1-(9-aminoanthracene)-N2-(2-methylpyridine)oxalamide Amine, N1,N2-bis(furan-2-ylmethyl)oxalamide, N1,N2-bis(2-thienylmethyl)-oxalamide, N1,N2-bis(4-hydroxy-2,6-dimethylphenyl)oxalamide, N1,N2-bis(4-hydroxy-2,6-diethylphenyl)oxalamide, N1-(4-hydroxy-2,6-diethylphenyl)-N2-(pyridin-2-ylmethyl)oxalamide, N1-(4-hydroxy-2,6-dimethylphenyl)-N2-(2-furanmethyl)oxalamide, N1-(2,6-dimethylphenyl)- N-(2,6-dimethylphenyl)-6-hydroxypicolinamide, N-(2,6-dimethylphenyl)-4-hydroxypicolinamide, N-(2,6-dimethylphenyl)-5-hydroxypicolinamide, 8-hydroxyquinoline, 1,10-phenanthroline, or a combination thereof.
4. The preparation method according to claim 1, characterized in that: The base is one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium phosphate, triethylamine, tripropylamine, diisopropylethylamine, DBU, DABCO, pyridine, 2-methylpyridine, 2,6-lutidine, and tetrabutylammonium hydroxide.
5. The preparation method according to claim 1, characterized in that: The solvent includes one or more of water, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, sulfolane, toluene, acetonitrile, alcohol solvents, ether solvents, ketone solvents, and ester solvents.
6. The preparation method according to claim 1, characterized in that: The amount of the copper salt is 0.001-0.5wt% of the compound of formula I, preferably 0.001-0.002wt%; the amount of the ligand is 0.001-0.5wt% of the compound of formula I, preferably 0.001-0.1wt%.
7. The preparation method according to claim 1, characterized in that: The mass ratio of the base to the compound of formula I is 5:1 to 1:5, preferably 2:1 to 1:
2.
8. The preparation method according to claim 1, characterized in that: The volume mass ratio of the solvent to the compound of formula I is 2-20 ml / g, preferably 4-10 ml / g.
9. The preparation method according to claim 1, characterized in that: The reaction temperature of the coupling reaction is 60-180°C, preferably 80-130°C.
10. The preparation method according to claim 1, characterized in that: The reaction time of the coupling reaction is 2-24 hours, preferably 8-10 hours.