Process for the preparation of n-[4,6-bis(heptadecoxy)-1,3,5-triazinane-2-yl]hexane-1,6-diamine

Abstract

The application belongs to the technical field of chemical synthesis, and specifically provides a preparation method of N-[4,6-bis(heptadecyloxy)-1,3,5-triazinyl-2-yl]hexane-1,6-diamine, which comprises the following steps: S1, performing ether exchange reaction of 2-chloro-4,6-dimethoxy-1,3,5-triazine and 9-heptadecanol to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine; S2, performing reaction of the 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine and an ammoniating reagent to generate 4,6-bis(heptadecyloxy)-1,3,5-triazin-2-amine; and S3, performing nucleophilic substitution reaction of the 4,6-bis(heptadecyloxy)-1,3,5-triazin-2-amine and 6-bromohexylamine hydrobromide to generate N-[4,6-bis(heptadecyloxy)-1,3,5-triazinyl-2-yl]hexane-1,6-diamine. According to the preparation method of the embodiment of the application, the reaction is mild, the selectivity is high, the yield is high, the by-products are few, the generated three wastes are few, and the route is feasible.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine. Background Technology

[0002] Peptide drugs have become a hot topic in drug research in recent years due to their moderate molecular weight, low immunogenicity, and high specificity. N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine, with its hydrophobic long alkyl chain and hydrophilic amino group, is of great significance for the liquid-phase synthesis of peptides.

[0003] Currently, the main method for synthesizing N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine is to first synthesize an intermediate using a cyanuric chloride, 9-heptadecyl alcohol, and sodium hydrogen system, and then react it with 1,6-hexanediamine to obtain the product. This process requires two column chromatography steps, and the yield is low with poor selectivity, making it unsuitable for industrial production. Summary of the Invention

[0004] In view of this, the purpose of this invention is to provide a method for preparing N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine that is safe, easy to operate, easy to control, and has a high overall yield.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: The method for preparing N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine according to an embodiment of the present invention includes the following steps: Step S1 involves reacting 2-chloro-4,6-dimethoxy-1,3,5-triazine with 9-heptadecyl alcohol via an ether exchange reaction to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine; Step S2 involves reacting the 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine with an amination reagent to generate 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine; In step S3, the 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine and 6-bromohexylamine hydrobromide undergo a nucleophilic substitution reaction to generate N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0006] According to some embodiments of the present invention, in step S1, the ether exchange reaction is carried out under the action of a catalyst, the catalyst being selected from one or more of sodium tert-butoxide, ferric chloride hexahydrate, magnesium isopropyl chloride, and ferric trifluoromethanesulfonate.

[0007] Further, step S1 includes: 2-Chloro-4,6-dimethoxy-1,3,5-triazine, 9-heptadecyl alcohol, and isopropyl magnesium chloride are added to tetrahydrofuran to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine. The molar ratio of 2-chloro-4,6-dimethoxy-1,3,5-triazine, 9-heptadecyl alcohol, and isopropyl magnesium chloride is 1.0:(2.0-2.5):(0.01-0.2). The reaction temperature is 20-30℃, and the reaction time is 3-5 h.

[0008] Further, in step S1, after the reaction is complete, the mixture is washed with an aqueous citric acid solution, separated, and concentrated to dryness to obtain the 2-chloro-4,6-bis(heptadecanoxy)-1,3,5-triazine.

[0009] According to some embodiments of the present invention, in step S2, the amination reagent is ammonia water, and step S2 includes: The 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine was added to methanol, and ammonia was added to react and generate the 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine.

[0010] Furthermore, the molar ratio of ammonia to 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine is (2.0-3.0):1.0, the ammonia is added at a temperature of 20-25°C, the reaction time is 2-6 hours, and the reaction temperature is 50-60°C.

[0011] Further, in step S2, after the reaction is complete, the mixture is filtered, slurried with water, filtered again, and dried to obtain the 4,6-bis(heptadecoxy)-1,3,5-triazine-2-amine.

[0012] According to some embodiments of the present invention, step S3 includes: The 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine and 6-bromohexylamine hydrobromide were added to tetrahydrofuran, and DBU was added dropwise to generate the N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0013] Further, the molar ratio of 4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-amine, 6-bromohexylamine hydrobromide, and DBU is 1.0:(1.0-1.5):(2.0-2.5), the temperature at which DBU is added is 0-5℃, the reaction time is 2-6 h, and the reaction temperature is 25-35℃.

[0014] Further, in step S3, after the reaction is complete, the mixture is concentrated to dryness, dissolved in ethyl acetate, washed with water, dried, and concentrated to dryness to obtain the N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0015] The above-described technical solution of the present invention has at least one of the following beneficial effects: The preparation method according to the embodiments of the present invention is characterized by mild reaction, high selectivity, high yield, few by-products, minimal waste generation, and strong route feasibility. Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention are within the scope of protection of the present invention.

[0017] The preparation method of N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine according to embodiments of the present invention is described in detail below.

[0018] The method for preparing N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine according to an embodiment of the present invention includes: Step S1 involves reacting 2-chloro-4,6-dimethoxy-1,3,5-triazine with 9-heptadecyl alcohol via an ether exchange reaction to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine; Step S2 involves reacting the 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine with an amination reagent to generate 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine; In step S3, the 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine and 6-bromohexylamine hydrobromide undergo a nucleophilic substitution reaction to generate N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0019] In other words, according to the preparation method of this application, 9-heptadecyl alcohol is reacted with 2-chloro-4,6-dimethoxy-1,3,5-triazine to generate the first intermediate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine, which then reacts with an amination reagent to generate the second intermediate 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine. Finally, it undergoes a nucleophilic substitution reaction with 6-bromohexylamine hydrobromide to generate N-[4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-yl]hexane-1,6-diamine. According to the preparation method of this application, the reaction conditions for each step are mild, the selectivity is high, the yield is high, and there are few byproducts. Furthermore, the purification of the intermediates at each step is simple and easy to operate, resulting in high product purity and strong route feasibility.

[0020] Below, each step will be explained in detail.

[0021] (a) Ether exchange reaction That is, the step of subjecting 2-chloro-4,6-dimethoxy-1,3,5-triazine to an ether exchange reaction with 9-heptadecyl alcohol to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine.

[0022] The existing preparation method uses cyanuric chloride as one of the raw materials to undergo a nucleophilic substitution reaction with 9-heptadecyl alcohol. The synthetic route has a slow reaction, poor selectivity, and is prone to producing byproducts of three or one 9-heptadecyl alcohol. Subsequent column chromatography is required to purify it to the intermediate. In addition, the second step of using 1,6-hexanediamine will also produce one or two byproducts, which must be purified to the final product by column chromatography.

[0023] To address this, this application involves an ether exchange reaction between 2-chloro-4,6-dimethoxy-1,3,5-triazine and 9-heptadecyl alcohol to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine, which exhibits high selectivity, high yield, few side reactions, and simple purification of the intermediate product.

[0024] According to some embodiments of the present invention, in step S1, the ether exchange reaction is carried out under the action of a catalyst, the catalyst being selected from one or more of sodium tert-butoxide, ferric chloride hexahydrate, magnesium isopropyl chloride, and ferric trifluoromethanesulfonate.

[0025] Under the action of a catalyst, 9-heptadecyl alcohol is first converted into a salt, which then reacts with 2-chloro-4,6-dimethoxy-1,3,5-triazine to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine. This avoids the situation of having three or one 9-heptadecyl alcohol byproducts in the prior art, resulting in higher selectivity and higher yield.

[0026] According to some embodiments of the present invention, step S1 includes: adding 2-chloro-4,6-dimethoxy-1,3,5-triazine, 9-heptadecyl alcohol, and isopropyl magnesium chloride to tetrahydrofuran to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine.

[0027] Specifically, the reaction is shown in equation (1) below: (1) When using isopropyl magnesium chloride as a catalyst, the reaction first involves magnesium chloride and 9-heptadecyl alcohol to form magnesium chloride-9-heptadecyl alcohol, which then reacts with 2-chloro-4,6-dimethoxy-1,3,5-triazine to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine. Using isopropyl magnesium chloride as a catalyst offers high selectivity, low cost, and the resulting intermediates are easily separated and purified.

[0028] The molar ratio of 2-chloro-4,6-dimethoxy-1,3,5-triazine, 9-heptadecyl alcohol, and isopropyl magnesium chloride can be 1.0:(2.0-2.5):(0.01-0.2), preferably 1.0:2.1:0.05. Using a slight excess of 9-heptadecyl alcohol, while the amount of 2-chloro-4,6-dimethoxy-1,3,5-triazine is slightly below the stoichiometric amount, is beneficial for improving the reaction rate and yield. The remaining 9-heptadecyl alcohol is easily removed during post-treatment.

[0029] The reaction temperature can be 20-30℃, and the reaction time can be 3-5 hours. In other words, the reaction conditions are mild, can be operated at room temperature, and have high efficiency.

[0030] Furthermore, in step S1, after the reaction is complete, the mixture is washed with an aqueous citric acid solution, separated, and concentrated to dryness to obtain the 2-chloro-4,6-bis(heptadecanoxy)-1,3,5-triazine. In other words, the intermediate only requires simple processing before it can be directly used in subsequent steps; purification is simple and easy to operate, produces less waste, and is low in cost.

[0031] (ii) Ammoniation reaction That is, the 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine is reacted with an amination reagent to generate 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine.

[0032] In other words, according to the preparation method of the present invention, after obtaining 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine through the above-mentioned ether exchange reaction, it is reacted with an amination reagent to generate 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine.

[0033] As an amination reagent, ammonia water, ammonia gas, or a mixture thereof can be used, for example.

[0034] According to some embodiments of the present invention, in step S2, the amination reagent is ammonia water, and step S2 includes: The 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine was added to methanol, and ammonia was added to react and generate the 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine.

[0035] In other words, the amino group replaces the chlorine at the 2-position of the triazine ring to generate the second intermediate, namely 4,6-bis(heptadecoxy)-1,3,5-triazine-2-amine.

[0036] Specifically, the reaction is shown in equation (2) below: (2) Further, the molar ratio of ammonia to 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine is (2.0-3.0):1.0. Using excess ammonia is beneficial for increasing the reaction rate and yield. Preferably, the molar ratio of ammonia to 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine is 2.5:1.0.

[0037] The ammonia solution can be added at a temperature of 20-25℃, the reaction time can be 2-6 hours, and the reaction temperature can be 50-60℃ (i.e., heating is carried out after the ammonia solution is added). The reaction conditions are mild and easy to operate.

[0038] Further, in step S2, after the reaction is complete, the mixture is filtered, slurried with water, filtered again, and dried to obtain the 4,6-bis(heptadecoxy)-1,3,5-triazine-2-amine.

[0039] (iii) Nucleophilic substitution reaction That is, after amination to obtain 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine, it is necessary to further undergo a nucleophilic substitution reaction with 6-bromohexylamine hydrobromide to generate the target product N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0040] According to some embodiments of the present invention, step S3 includes: The 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine and 6-bromohexylamine hydrobromide were added to tetrahydrofuran, and DBU was added dropwise to generate the N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0041] DBU is a strong organic base, but its nucleophilicity is very weak. It acts as an effective acid-binding agent in the system without undergoing nucleophilic side reactions, which is beneficial for improving reaction yield. Using other organic or inorganic bases, however, will more or less produce byproducts, affecting product quality and yield.

[0042] Specifically, the reaction is shown in equation (3) below: (3) Further, the molar ratio of 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine, 6-bromohexylamine hydrobromide, and DBU is 1.0:(1.0-1.5):(2.0-2.5). Preferably, the molar ratio is 1.0:1.0:2.0. Feeding according to the above molar ratio ensures complete conversion of the raw materials, avoiding waste of excess raw materials.

[0043] Furthermore, the temperature for adding DBU can be set to 0-5℃, the reaction time to 2-6 h, and the reaction temperature to 25-35℃.

[0044] Further, in step S3, after the reaction is complete, the mixture is concentrated to dryness, dissolved in ethyl acetate, washed with water, dried, and concentrated to dryness to obtain the N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0045] As can be seen from the above description, the reaction conditions for each step of this application are mild, simple and easy to perform, with few side reactions, and the purification of intermediates is simple, easy to operate, and safe and reliable.

[0046] To enable those skilled in the art to better understand the technical solution of the present invention, the preparation method of N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine of the present invention will be further described in detail below with reference to specific embodiments.

[0047] Example 1 Step 1: Take a 500ml three-necked flask and add THF (200ml, 5P) and 9-heptadecyl alcohol (122.75g, 0.478mol, 2.1eq). While maintaining the temperature at 20℃, add a THF solution containing isopropyl magnesium chloride (2mol / L, 1.17g, 0.011mol, 0.05eq) and stir for 0.5h. Finally, add 2-chloro-4,6-dimethoxy-1,3,5-triazine (40g, 0.228mol, 1.0eq) all at once, and react at 20-30℃ for 3h. After the reaction is complete as monitored by TLC, quench with 200ml of 1mol / L citric acid aqueous solution, separate the layers, concentrate to dryness, and obtain 135.3g of 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine, yield 95.1%.

[0048] Step 2: Take a 500ml three-necked flask and add methanol (240ml, 4P) and 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine (60g, 0.096mol, 1.0eq). Add 25% ammonia water (33.7g, 0.24mol, 2.5eq) while maintaining the temperature at 20℃. After the addition is complete, raise the temperature to 55℃ and react for 4 h. After the reaction is complete, filter, slurry the solid with water, filter, and dry to obtain 54.2g of 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine, with a yield of 93.2%.

[0049] Step 3: Take a 500ml three-necked flask and add THF (150ml, 3P) and 4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-amine (50g, 0.08mol, 1.0eq), 6-bromohexylamine hydrobromide (21.5g, 0.08mol, 1.0eq). While maintaining the temperature at 0-5℃, add DBU dropwise (25.16g, 0.16mol, 2.0eq). After the addition is complete, raise the temperature to 25-35℃ and react for 4 h. After the reaction is complete, concentrate to dryness. Dissolve the organic phase in 300ml of ethyl acetate, wash with 150ml of water, separate the layers, dry the organic phase, and concentrate to dryness to obtain 54.19g of N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine, yield 93%, HPLC: 99.8%.

[0050] The structure of the obtained product was confirmed by nuclear magnetic resonance (NMR) experiments, and the data are as follows: 1H NMR (500 MHz, CDCl3) δ 5.57–5.59 (t, 1H), 5.09–5.17 (m,2H), 3.37–3.41 (dd, 2H), 2.65–2.68 (t, 2H), 1.55–1.67 (m, 10H) ,1.22–1.44 (m, 56H),0.83–0.86 (t, 12H).

[0051] The detection results are consistent with the structure of N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0052] Example 2 Step 1: In a 2L three-necked flask, add 800ml of THF (5P) and 9-heptadecyl alcohol (491g, 1.91mol, 2.1eq). While maintaining the temperature at 20℃, add a THF solution containing isopropyl magnesium chloride (2mol / L, 4.68g, 0.045mol, 0.05eq) and stir for 0.5h. Finally, add 160g of 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.911mol, 1.0eq) all at once, and react at 20-30℃ for 3h. After the reaction is complete as monitored by TLC, quench with 800ml of 1mol / L citric acid aqueous solution, separate the layers, concentrate to dryness, and obtain 546.5g of 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine, with a yield of 96%.

[0053] Step 2: Take a 2L three-necked flask and add methanol (960ml, 4P) and 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine (240g, 0.384mol, 1.0eq). Add 25% ammonia water (134.7g, 0.96mol, 2.5eq) while maintaining the temperature at 20℃. After the addition is complete, raise the temperature to 55℃ and react for 4 h. After the reaction is complete, filter, slurry the solid and water, filter, and dry to obtain 220.9g of 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine, with a yield of 95%.

[0054] Step 3: Take a 2L three-necked flask and add THF (600ml, 3P) and 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine (200g, 0.329mol, 1.0eq) and 6-bromohexylamine hydrobromide (86g, 0.329mol, 1.0eq). Control the temperature at 0-5℃ and add DBU (100.65g, 0.661mol, 2.0eq) dropwise. After the addition is complete, raise the temperature to 25-35℃ and react for 4 h. After the reaction is complete, concentrate to dryness. Dissolve the organic phase in 1.2L ethyl acetate and wash with 600ml of water. Separate the liquid and dry the organic phase. Concentrate to dryness to obtain 223.9g of N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine, yield 96.2%, HPLC: 99.8%.

[0055] The structure of the obtained product was confirmed by nuclear magnetic resonance (NMR) experiments, and the data are as follows: 1 H NMR (500 MHz, CDCl3) δ 5.57–5.59 (t, 1H), 5.09–5.17 (m,2H), 3.37–3.41 (dd, 2H), 2.65–2.68 (t, 2H), 1.55–1.67 (m, 10H) ,1.22–1.44 (m, 56H),0.83–0.86 (t, 12H).

[0056] The detection results are consistent with the structure of N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

[0057] In summary, the method for preparing N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine of the present invention has high selectivity, high reaction yield, few side reactions, simple and easy purification of intermediates, and the obtained product has a high liquid chromatography purity of up to 99.8%, and is safe and reliable.

[0058] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine, characterized in that, Includes the following steps: Step S1 involves reacting 2-chloro-4,6-dimethoxy-1,3,5-triazine with 9-heptadecyl alcohol via an ether exchange reaction to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine; Step S2 involves reacting the 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine with an amination reagent to generate 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine; In step S3, the 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine and 6-bromohexylamine hydrobromide undergo a nucleophilic substitution reaction to generate N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

2. The preparation method according to claim 1, characterized in that, In step S1, the ether exchange reaction is carried out under the action of a catalyst, which is selected from one or more of sodium tert-butoxide, ferric chloride hexahydrate, magnesium isopropyl chloride, and ferric trifluoromethanesulfonate.

3. The preparation method according to claim 2, characterized in that, Step S1 includes: 2-Chloro-4,6-dimethoxy-1,3,5-triazine, 9-heptadecyl alcohol, and isopropyl magnesium chloride are added to tetrahydrofuran to generate 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine. The molar ratio of 2-chloro-4,6-dimethoxy-1,3,5-triazine, 9-heptadecyl alcohol, and isopropyl magnesium chloride is 1.0:(2.0-2.5):(0.01-0.2). The reaction temperature is 20-30℃, and the reaction time is 3-5 h.

4. The preparation method according to claim 2, characterized in that, In step S1, after the reaction is complete, the mixture is washed with citric acid aqueous solution, separated, concentrated to dryness, and then the 2-chloro-4,6-bis(heptadecanoxy)-1,3,5-triazine is obtained.

5. The preparation method according to claim 1, characterized in that, In step S2, the amination reagent is ammonia water, and step S2 includes: The 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine was added to methanol, and ammonia was added to react and generate the 4,6-bis(heptadecyloxy)-1,3,5-triazine cyclo-2-amine.

6. The preparation method according to claim 5, characterized in that, The molar ratio of ammonia to 2-chloro-4,6-bis(heptadecyloxy)-1,3,5-triazine is (2.0-3.0):1.0, the ammonia is added at 20-25℃, the reaction time is 2-6 hours, and the reaction temperature is 50-60℃.

7. The preparation method according to claim 5, characterized in that, In step S2, after the reaction is complete, the mixture is filtered, slurried with water, filtered again, and dried to obtain the 4,6-bis(heptadecoxy)-1,3,5-triazine-2-amine.

8. The preparation method according to claim 1, characterized in that, Step S3 includes: The 4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-amine and 6-bromohexylamine hydrobromide were added to tetrahydrofuran, and DBU was added dropwise to generate the N-[4,6-bis(heptadecyloxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

9. The preparation method according to claim 8, characterized in that, The molar ratio of 4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-amine, 6-bromohexylamine hydrobromide, and DBU is 1.0:(1.0-1.5):(2.0-2.5), the temperature at which DBU is added is 0-5℃, the reaction time is 2-6 h, and the reaction temperature is 25-35℃.

10. The preparation method according to claim 8, characterized in that, In step S3, after the reaction is complete, the mixture is concentrated to dryness, dissolved in ethyl acetate, washed with water, dried, and concentrated to dryness to obtain the N-[4,6-bis(heptadecoxy)-1,3,5-triazinecyclo-2-yl]hexane-1,6-diamine.

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