A kind of preparation method of azelaic acid amide

Abstract

The present invention relates to the technical field of drug synthesis, and discloses a method for preparing azelaic acid diamide compound, comprising the following steps: (1) using azelaic acid monomethyl ester, i.e. compound I, as a starting reactant, reacting with 2-haloethylamine to obtain compound II; (2) using compound II and formate as reaction raw materials, and methanol as a solvent, and performing a one-step reaction to obtain compound III, i.e. azelaic acid diamide MEA. Compared with the prior art route, the synthesis process of the present invention is simple to operate, has cheap raw materials, mild reaction conditions, high product purity and yield, is suitable for industrial production, and has great industrial prospects.

Description

Technical Field

[0001] The invention relates to the technical field of drug synthesis, in particular to a method for preparing azelaic acid amide compound. Background Art

[0002] Azelaic acid MEA is a new type of sebum balancer, suitable for the care of oily and seborrheic skin. Azelaic acid MEA is a derivative of azelaic acid, which has the same biological activity as azelaic acid, but does not have the inherent disadvantages of azelaic acid such as poor solubility in water / oil, destruction of the emulsification system, difficulty in exerting the effect, and high irritation. The effects of azelaic acid MEA include: 1. Helping oily skin, seborrheic skin, and skin with multiple melasma to maintain the balance of oil secretion; 2. Can be used in cosmeceuticals for the treatment of acne and blackheads, and is effective against Propionibacterium acnes, Corynebacterium and Staphylococcus epidermidis; 3. Has a good whitening effect and can be used to treat spots and chloasma; 4. Used in conjunction with pyridoxine and zinc, it can inhibit 5-alpha reductase; 5. Has a good exfoliating (dead skin removal) effect; 6. Can be used to treat rosacea (red spots and papulopustular rosacea).

[0003] Currently, it is reported that there are two methods for synthesizing azelaic acid amide MEA:

[0004] Method 1: Azelaic anhydride is directly reacted with ethanolamine to form amide (Organic Preparation and Procedures International, 2013, vol. 45, #4, p. 314-320).

[0005] Method 2: First, attach a protective group to the hydroxyl group of ethanolamine, and then react with acyl chloride to form amide (WO2007 / 88999, 2007, A1)

[0006] Of the above two methods, the azelaic anhydride in method 1 is difficult to synthesize and has a low yield. The process of attaching a protecting group to the hydroxyl group of ethanolamine in method 2 and removing the protecting group is quite complicated and is not conducive to industrial production. Summary of the invention

[0007] Therefore, it is necessary to provide a method for preparing azelaic acid amide compound to solve the problem that the existing azelaic acid amide MEA is difficult to synthesize and has a low yield.

[0008] To achieve the above object, the present invention provides the following technical solutions. The present invention provides a method for preparing azelaic acid amide compound, comprising the following steps:

[0009] (1) using azelaic acid monomethyl ester, i.e. compound I, as the starting reactant, and reacting with 2-haloethylamine to obtain compound II,

[0010] (2) Compound II and formate are used as reaction raw materials, methanol is used as solvent, and compound III is obtained by one-step reaction, namely, azelaic acid amide MEA.

[0011] The reaction formula is as follows:

[0012]

[0013] Wherein X is a halogen element.

[0014] In some embodiments, during the process of compound I synthesizing compound II, the organic solvent is one or more of alcohols, organic amines, and alicyclic hydrocarbons.

[0015] In some embodiments, during the process of compound I synthesizing compound II, the alcohol is methanol.

[0016] In some embodiments, in step (1), the molar ratio of monomethyl azelaic acid ester to 2-haloethylamine is 1:1.1-1:2, the reaction temperature is 35°C-65°C, and the reaction time is 2h-8h.

[0017] In some embodiments, in step (1), the molar ratio of monomethyl azelaic acid ester to 2-haloethylamine is 1:1.3-1:1.5, the reaction temperature is 40°C-60°C, and the reaction time is 2h-3h.

[0018] The setting of feed ratio, reaction temperature and reaction time will affect the yield and purity of the compound. In this article, the preferred reaction conditions are that the molar ratio of monomethyl azelaic acid and 2-haloethylamine is 1:1.3-1:1.5, the reaction temperature is 40°C-60°C, and the reaction time is 2h-3h, so that the purity of the prepared compound can reach more than 95%, and the yield of the compound in step (1) can reach more than 80%.

[0019] In some embodiments, the 2-haloethylamine is selected from 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride.

[0020] In some embodiments, an organic base is added in step (1) as an acid-binding agent. The acid-binding agent can neutralize the acid generated in step (1), thereby promoting the reaction in step (1).

[0021] In some embodiments, the acid binding agent may be triethylamine, DIEA or pyridine, and the molar ratio of the acid binding agent to the monomethyl azelate (Compound I) is 1:2.0-1:3, preferably 1:2.3-1:2.5.

[0022] In some embodiments, after the reaction in step (1) is completed, the solvent is evaporated under reduced pressure, water is added to dissolve, acid is added to adjust the pH, and then extraction is performed and rotary evaporation is performed to obtain compound II. In step (1) of the present invention, by controlling the reaction conditions, the reaction product is made single, and the reaction product can reach a purity of more than 95% after simple acid adjustment and extraction without further purification treatment.

[0023] In some embodiments, in step (2), the molar ratio of compound II to formate is 1:0.95-1:2.05, the reaction temperature is 35°C-65°C, and the reaction time is 4h-10h.

[0024] In some embodiments, in step (2), the molar ratio of compound II to formate is 1:1-1:2, the reaction temperature is 40°C-60°C, and the reaction time is 5h-6h.

[0025] The setting of feed ratio, reaction temperature and reaction time will affect the yield and purity of the compound. In this article, the preferred reaction conditions are that the molar ratio of compound II and formate is 1:1-1:2, the reaction temperature is 40°C-60°C, and the reaction time is 5h-6h, so that the purity of the prepared compound can reach more than 98%, and the yield of the compound in step (2) can reach more than 80%.

[0026] In some embodiments, the formate salt is potassium formate or sodium formate.

[0027] In some embodiments, in step (2), after the reaction between compound II and formate is completed, the methanol solvent is evaporated under reduced pressure, water is added to cool, and the nonanediamide compound is precipitated.

[0028] In step (2) of the present invention, the reaction conditions are controlled so that the reaction product is single and the reaction product can reach a purity of more than 98.5% by simply adding water and precipitating it without further purification treatment.

[0029] In some embodiments, water is added to cool to 10-20°C.

[0030] The above technical solution has the following beneficial effects:

[0031] In the present invention, monomethyl azelaic acid is used as a raw material to obtain azelaic acid amide compound MEA with high yield and high purity through two-step reaction. The total yield of the two reaction steps can be above 70%. The intermediate product compound II and the final reaction product compound III can be obtained by simple extraction and precipitation with water to obtain a compound with a purity of more than 95%.

[0032] In the step (1) of the present invention, the reaction temperature and reaction conditions of monomethyl azelaic acid and 2-haloethylamine are controlled so that the product is a single-end aminolysis product of monomethyl azelaic acid, and in the step (2), methanol is used as a solvent, compound II and formate first undergo a substitution reaction, and then thermal decomposition of the ester occurs, thereby preparing azelaic acid amide compound MEA with high purity and high yield.

[0033] Terminology

[0034] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that the process, method, article or terminal device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or terminal device. In the absence of further restrictions, the elements defined by the sentence "include..." or "comprise..." do not exclude the existence of other elements in the process, method, article or terminal device including the elements. In addition, in this article, "greater than", "less than", "exceed" and the like are understood to exclude the number itself; "above", "below", "within" and the like are understood to include the number itself.

[0035] In the present invention, "room temperature" or "normal temperature" refers to the ambient temperature, which is from about 10°C to about 40°C. In some embodiments, "room temperature" or "normal temperature" refers to a temperature from about 20°C to about 30°C; in other embodiments, "room temperature" or "normal temperature" refers to a temperature from about 25°C to about 30°C; in still other embodiments, "room temperature" or "normal temperature" refers to 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, etc.

[0036] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 This is the NMR image of MEA azelaic acid amide prepared in Example 1.

[0038] Figure 2 This is the MS mass spectrum of azelaic acid amide MEA prepared in Example 1. DETAILED DESCRIPTION

[0039] In order to explain the technical content, structural features, achieved objectives and effects of the technical solution in detail, the following is a detailed description in conjunction with specific embodiments.

[0040] Embodiment 1:

[0041] In a 100mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 12.65g (0.125mol) of triethylamine, 20.0g of methanol, 10.10g (0.050mol) of monomethyl azelate, and 15.37g (0.075mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 60°C and reacted at this temperature for 3 hours. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the monomethyl azelate spot was the end point of the reaction. After the reaction was completed, methanol was evaporated under reduced pressure at 60°C, water was added to dissolve, and 85% phosphoric acid was added after stirring and dissolving, and the pH value was adjusted to 5-6. The mixed solution was extracted with dichloromethane, and the extract was dried at 50°C to obtain about 13g of a white product (Compound II), with a purity greater than 95% and a yield of 88.38%.

[0042] The above white product (Compound II) was mixed with 4.62 g (0.055 mol) of potassium formate and 50 g of methanol, and the mixture was heated to 60°C and reacted at this temperature for 6 hours. The reaction was detected by TLC (developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the spots of the product (Compound II) was regarded as the end point of the reaction. After the reaction was completed, the methanol was evaporated under reduced pressure at 60°C, 50 g of water was added, and the mixture was cooled to 10-20°C to precipitate the product (Compound III), which was filtered and washed with ice water. After drying, 8.5 g of white powder of the product (Compound III) was obtained, with a purity of 98.3%, a yield of 83.17% in step (2), and a total yield of 73.5%.

[0043] The reaction formula is as follows

[0044]

[0045] Embodiment 2:

[0046] In a 500mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 58.18g (0.575mol) of triethylamine, 120g of methanol, 50.50g (0.250mol) of monomethyl azelate, and 66.58g (0.325mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 60°C and reacted at this temperature for 3 hours. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the monomethyl azelate spot was the end point of the reaction. After the reaction was completed, methanol was evaporated under reduced pressure at 60°C, water was added to dissolve, and 85% phosphoric acid was added after stirring and dissolving, and the pH value was adjusted to 5-6. The mixed solution was extracted with dichloromethane, and the extract was dried at 50°C to obtain about 60g of a white product (Compound II), with a purity greater than 95% and a yield of 81.58%.

[0047] The above white product (Compound II) was mixed with 23.13 g (0.275 mol) of potassium formate and 250 g of methanol, and the mixture was heated to 60°C and reacted at this temperature for 6 hours. The reaction was detected by TLC (developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the spots of the product (Compound II) was the end point of the reaction. After the reaction was completed, the methanol was evaporated under reduced pressure at 60°C, 50 g of water was added, and the mixture was cooled to 10-20°C to precipitate the product (Compound III), which was filtered and washed with ice water. After drying, 44.59 g of white powder of the product (Compound III) was obtained, with a purity of 98.5%, a yield of 94.53%, and a total yield of 77.1%.

[0048] Embodiment 3:

[0049] In a 100mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 11.6g (0.115mol) of triethylamine, 20.0g of methanol, 10.10g (0.050mol) of monomethyl azelate, and 13.33g (0.065mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 60°C and reacted at this temperature for 2 hours. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the monomethyl azelate spot was the end point of the reaction. After the reaction was completed, methanol was evaporated under reduced pressure at 60°C, water was added to dissolve, and 85% phosphoric acid was added after stirring and dissolving, and the pH value was adjusted to 5-6. The mixed solution was extracted with dichloromethane, and the extract was dried at 50°C to obtain about 13.2g of a white product (Compound II), with a purity greater than 95% and a yield of 89.73%.

[0050] Embodiment 4:

[0051] In a 250mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 25.3g (0.25mol) of triethylamine, 40.0g of methanol, 20.20g (0.1mol) of monomethyl azelate, and 30.75g (0.15mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 40°C and reacted at this temperature for 3 hours. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the monomethyl azelate spot was the end point of the reaction. After the reaction was completed, methanol was evaporated under reduced pressure at 60°C, water was added to dissolve, and 85% phosphoric acid was added after stirring and dissolving, and the pH value was adjusted to 5-6. The mixed solution was extracted with dichloromethane, and the extract was dried at 50°C to obtain about 26.5g of a white product (Compound II), with a purity greater than 95% and a yield of 90.07%.

[0052] Embodiment 5:

[0053] In a 100mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 10.12g (0.1mol) of triethylamine, 20.0g of methanol, 10.10g (0.050mol) of monomethyl azelate, and 11.3g (0.055mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 65°C and reacted at this temperature for 2 hours. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the monomethyl azelate spot was the end point of the reaction. After the reaction was completed, methanol was evaporated under reduced pressure at 60°C, water was added to dissolve, and 85% phosphoric acid was added after stirring and dissolving, and the pH value was adjusted to 5-6. The mixed solution was extracted with dichloromethane, and the extract was dried at 50°C to obtain about 12.2g of a white product (Compound II), with a purity greater than 90% and a yield of 82.94%.

[0054] Embodiment 6:

[0055] In a 100mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 15.18.g (0.15mol) of triethylamine, 20.0g of methanol, 10.10g (0.050mol) of monomethyl azelate, and 20.5g (0.1mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 60°C and reacted at this temperature for 3 hours. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the monomethyl azelate spot was the end point of the reaction. After the reaction was completed, methanol was evaporated under reduced pressure at 60°C, water was added to dissolve, and 85% phosphoric acid was added after stirring and dissolving, and the pH value was adjusted to 5-6. The mixed solution was extracted with dichloromethane, and the extract was dried at 50°C to obtain about 12.4g of a white product (Compound II), with a purity greater than 90% and a yield of 84.30%.

[0056] Comparative Example 1:

[0057] In a 100mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 12.65g (0.125mol) of triethylamine, 20.0g of methanol, 10.10g (0.050mol) of monomethyl azelate, and 30.75g (0.15mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 60°C and reacted at this temperature for 3 hours. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the monomethyl azelate spot was the end point of the reaction. After the reaction was completed, methanol was evaporated under reduced pressure at 60°C, water was added to dissolve, and 85% phosphoric acid was added after stirring and dissolving, and the pH value was adjusted to 5-6. The mixed solution was extracted with dichloromethane, and the extract was dried at 50°C to obtain about 13.1g of a white product (Compound II), with a purity of less than 85% and a yield of 89.06%.

[0058] Comparative Example 2:

[0059] In a 100mL single-mouth bottle equipped with a mechanical stirrer and a thermometer, 12.65g (0.125mol) of triethylamine, 20.0g of methanol, 10.10g (0.050mol) of monomethyl azelate, and 10.25g (0.05mol) of 2-bromoethylamine hydrobromide were added in sequence, and the mixture was heated to 60°C and reacted at this temperature. The reaction was detected by TLC (the developing solvent was petroleum ether / ethyl acetate (volume ratio 4:1). The experimental results showed that monomethyl azelate could not react completely.

[0060] Example 7

[0061] Take compound II 14.7g (0.05mol, purity greater than 95%) and potassium formate 4.2g (0.05mol), methanol 50g, mix, heat the mixture to 60℃, and react at this temperature for 5 hours. The reaction is detected by TLC (developing solvent is petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the product (compound II) spot is the end point of the reaction. After the reaction is completed, methanol is evaporated under reduced pressure at 60℃, 50g of water is added, cooled to 10-20℃, the product (compound III) is precipitated, filtered and washed with ice water, and dried to obtain 10.4g of white powder of the product (compound III), purity 97.2%, yield 89.99%.

[0062] Example 8

[0063] Take compound II 29.4g (0.1mol, purity greater than 95%) and potassium formate 16.8g (0.2mol), methanol 100g, mix, heat the mixture to 40℃, and react at this temperature for 6 hours. The reaction is detected by TLC (developing solvent is petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the spots of the product (compound II) is the end point of the reaction. After the reaction is completed, methanol is evaporated under reduced pressure at 60℃, 100g of water is added, cooled to 10-20℃, the product (compound III) is precipitated, filtered and washed with ice water, and dried to obtain 22.1g of white powder of the product (compound III), purity 95.2%, yield 95.6%.

[0064] Example 9

[0065] Take compound II 14.7g (0.05mol, purity greater than 95%) and potassium formate 4.0g (0.0476mol), methanol 50g, mix, heat the mixture to 35°C, and react at this temperature for 10 hours. The reaction is detected by TLC (developing solvent is petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the product (compound II) spot is the end point of the reaction. After the reaction is completed, methanol is evaporated under reduced pressure at 60°C, 50g of water is added, and the mixture is cooled to 10-20°C to precipitate the product (compound III), which is filtered and washed with ice water. After drying, the product (compound III) is obtained as a white powder 9.6g, with a purity of 92.8% and a yield of 83.07%.

[0066] Example 10

[0067] Take compound II 14.7g (0.05mol, purity greater than 95%) and potassium formate 8.61g (0.1025mol), methanol 50g, mix, heat the mixture to 65℃, and react at this temperature for 4 hours. The reaction is detected by TLC (developing solvent is petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the product (compound II) spot is the end point of the reaction. After the reaction is completed, methanol is evaporated under reduced pressure at 60℃, 50g of water is added, cooled to 10-20℃, the product (compound III) is precipitated, filtered and washed with ice water, and dried to obtain 9.8g of white powder of the product (compound III), with a purity of 88.5% and a yield of 84.80%.

[0068] Comparative Example 3

[0069] Take compound II 14.7g (0.05mol, purity greater than 95%) and potassium formate 3.8g (0.045mol), methanol 50g, mix, heat the mixture to 60°C, and react at this temperature for 5 hours. The reaction is detected by TLC (developing solvent is petroleum ether / ethyl acetate (volume ratio 4:1), methanol is evaporated under reduced pressure at 60°C, 50g of water is added, cooled to 10-20°C, the product (compound III) is precipitated, filtered and washed with ice water, and dried to obtain 8.7g of white powder of the product (compound III), purity 84.3%, yield 75.28%.

[0070] Comparative Example 4

[0071] Take compound II 14.7g (0.05mol, purity greater than 95%) and potassium formate 10.5g (0.125mol), methanol 50g, mix, heat the mixture to 60℃, and react at this temperature for 5 hours. The reaction is detected by TLC (developing solvent is petroleum ether / ethyl acetate (volume ratio 4:1), and the disappearance of the spots of the product (compound II) is the end point of the reaction. After the reaction is completed, methanol is evaporated under reduced pressure at 60℃, 50g of water is added, cooled to 10-20℃, the product (compound III) is precipitated, filtered and washed with ice water, and dried to obtain 9.5g of white powder of the product (compound III), with a purity of 83.4% and a yield of 82.20%.

[0072] In the present invention, in step (1), the reaction temperature and reaction conditions of monomethyl azelaic acid and 2-haloethylamine are controlled so that the product is a single-end aminolysis product of monomethyl azelaic acid, and in step (2), methanol is used as a solvent, compound II and formate first undergo a substitution reaction, and then thermal decomposition of the ester occurs, thereby preparing azelaic acid diamide compound MEA with high purity and high yield. In the present invention, by screening conditions such as feed ratio and reaction temperature, the reaction product can maintain a high yield and high purity.

[0073] Although the above embodiments have been described, once those skilled in the art know the basic creative concepts, they can make additional changes and modifications to these embodiments. Therefore, the above description is only an embodiment of the present invention and does not limit the patent protection scope of the present invention. Any equivalent structure or equivalent process transformation made by using the contents of the specification and drawings of the present invention, or directly or indirectly used in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A method for preparing azelaic acid amide compound, characterized in that: The steps include: (1) Using monomethyl azelaic acid, i.e. compound I, as the starting reactant, reacting with 2-haloethylamine to obtain compound II, (2) Compound II and formate are used as reaction materials, methanol is used as solvent, and compound III is obtained by one-step reaction, i.e., azelaic acid amide compound. The reaction formula is as follows: ； ； Wherein X is a halogen element; In step (1), the molar ratio of azelaic acid monomethyl ester to 2-haloethylamine is 1:1.1-1:2, the reaction temperature is 35°C-65°C, and the reaction time is 2h-8h; In step (2), the molar ratio of compound II to formate is 1:0.95-1:2.05, the reaction temperature is 35°C-65°C, and the reaction time is 4h-10h.

2. The method for preparing azelaic acid amide compound according to claim 1, characterized in that: In step (1), the molar ratio of monomethyl azelaic acid to 2-haloethylamine is 1:1.3-1:1.5, the reaction temperature is 40°C-60°C, and the reaction time is 2h-3h.

3. The method for preparing azelaic acid amide compound according to claim 1, characterized in that: The 2-haloethylamine is selected from 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride.

4. The method for preparing azelaic acid amide compound according to claim 1, characterized in that: In step (1), an organic base is added as an acid binding agent.

5. The method for preparing azelaic acid amide compound according to claim 1, characterized in that: In step (2), the molar ratio of compound II to formate is 1:1-1:2, the reaction temperature is 40°C-60°C, and the reaction time is 5h-6h.

6. The method for preparing azelaic acid amide compound according to claim 1, characterized in that: The formate is potassium formate or sodium formate.

7. The method for preparing azelaic acid amide compound according to claim 1, characterized in that: In step (2), after the reaction between compound II and formate is completed, the methanol solvent is evaporated under reduced pressure, water is added to cool, and the nonanamide compound is precipitated.

8. The method for preparing azelaic acid amide compound according to claim 7, characterized in that: Add water and cool to 10-20℃.

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