Preparation method of amine compound
Through the Mitsunobu reaction and other organic response steps, the amine compound preparation route was simplified, and the problems of preparation of the long and harsh conditions in the existing methods were solved. Synthetic provides the foundation.
Patent Information
- Application Number
- CN202411501101.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-25
- Publication Date
- 2025-01-28
AI Technical Summary
The existing preparation methods for amine compounds used for the synthesis of trisitine cysteine have a long preparation route and are harsh in the conditions used, which affects the synthesis efficiency and cost.
The Mitsunobu reaction is used to build the C-N key. PD/C catalytic hydrogenation and Fischer esterization reactions are performed by commercialized reagent mustard acid 1, combined with TBSCL, DIBAL, MITSUNOBU coupling and other steps to synthesize amine compounds.
Simplify the synthetic route, reduce the cost of reaction, the conditions of use are mild, the experiment is simple, and the amino compound is obtained with a better income yield, which provides the foundation for the synthesis of triple fir.
Smart Images
Figure CN119371396A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of catalytic synthesis, and particularly relates to a method for preparing an amine compound. Background Art
[0002] Many natural products contain amine groups to form nitrogen-containing heterocyclic compounds, such as cephalotaxine, morphine, quinine, etc. These compounds play an important role in the field of medicine. The ester-base compounds derived from the natural product cephalotaxine mentioned above can treat leukemia. Cephalotaxus alkaloids are a class of natural products isolated from Cephalotaxus plants. To date, nearly 100 cephalotaxine-type alkaloids have been isolated and identified, and some ester-base natural products have significant anti-tumor activity, such as homoharringtonine and cephalotaxine among the ester-base derivatives. At present, the ester-base derivative of cephalotaxine, homoharringtonine, has entered the market as a drug at home and abroad. The main way to obtain it is to extract it from plants or to obtain it through semi-synthesis of cephalotaxine.
[0003] The hypothesis of the biosynthesis route of perhartmannine proposed by Parry in 1980 involved amine compounds, but the preparation method of this amine compound has a long preparation route and harsh conditions, which affects the biosynthesis of perhartmannine. Summary of the invention
[0004] The present invention provides a method for preparing amine compounds in order to solve the problems that the current method for preparing amine compounds for synthesizing cephalotaxine has a long preparation route and relatively harsh conditions.
[0005] The present invention uses Mitsunobu reaction to construct CN bond as a key synthesis strategy to synthesize amine linear compounds. The synthesis route uses commercial reagent sinapinic acid 1 as a raw material, synthesizes compound 2 through catalytic hydrogenation and Fischer esterification reaction, and compound 2 reacts with TBSCl and DIBAL to obtain compound 4. Compound 4 and compound 5 undergo Mitsunobu coupling reaction to obtain amine compound 6 with a yield of 88%. Compound 6 is subjected to p-tert-butylthiophenol to remove the Ns protecting group and TBAF to remove the TBS protecting group to obtain an amine compound.
[0006] A method for preparing an amine compound is carried out according to the following steps:
[0007] 1. Sinapic acid was subjected to Pd / C catalytic hydrogenation and Fischer esterification to obtain compound 2;
[0008] 2. Compound 2 and imidazole were added to a reaction bottle, dichloromethane was added under ice bath conditions, tert-butyldimethylsilyl chloride was added after dissolution, the temperature was raised to room temperature, the reaction was quenched after the reaction was complete, and then the organic solvent was removed by extraction and rotary evaporation, and the compound 3 was obtained after separation and purification;
[0009] 3. Compound 3 was added to a reaction tube, treated with anhydrous and oxygen-free conditions three times, then filled with nitrogen, and then dichloromethane was added, stirred to dissolve, and then continued to stir under ice bath conditions, and diisobutylaluminum hydride was added dropwise, and the reaction system was kept at 0°C. After the reaction was completed, a saturated sodium potassium tartrate solution and ethyl acetate were added and stirred until the reaction system was clear, and then extracted, and the organic solvent was removed by rotary evaporation, and separated and purified to obtain compound 4;
[0010] 4. At room temperature, piperidine reacts with p-nitrobenzenesulfonyl chloride and sodium carbonate in tetrahydrofuran solution to obtain compound 5;
[0011] 5. Compound 4, compound 5 and triphenylphosphine were added to the reaction tube, and nitrogen was filled after the anhydrous and oxygen-free treatment was completed. Xylene was added, and the mixture was placed in an ice bath and stirred. Diisopropyl azodicarboxylate was added dropwise. After the reaction was completed, the organic solvent was removed by rotary evaporation, and the mixture was separated and purified to obtain compound 6;
[0012] 6. Compound 6 and potassium carbonate were added to a glass bottle, and then N,N-dimethylformamide was added. After stirring and dissolving, p-methylthiophenol was added. After the reaction was completed, the reaction was quenched, and the organic phase was extracted and washed. N,N-dimethylformamide was removed by rotary evaporation, and then separated and purified to obtain compound 7;
[0013] 7. Add compound 7 to a reaction bottle, add tert-butyldimethylsilyl chloride, and then add tetrahydrofuran, stir at room temperature, quench the reaction after the reaction is completed, extract, and remove the solvent by rotary evaporation of the organic phase, separate and purify to obtain an amine compound.
[0014] Reaction route of the present invention:
[0015]
[0016] Beneficial effects of the present invention:
[0017] The invention starts from a commercial reagent sinapinic acid 1, and obtains compound 2 with a yield of 97% through Pd / C catalytic hydrogenation and Fischer esterification reaction, and then obtains compound 3 by adding TBS protective group to phenolic hydroxyl group under the action of imidazole and TBSCl. The ester group of compound 3 reacts with DIBAL to undergo reduction to obtain alcohol compound 4, and the compound undergoes Mitsunobu reaction with compound 5. During the reaction, solvent screening (MeCN, THF, Xylene) is performed, and it is found that compound 6 is obtained with a yield of 88% when Xylene is used as solvent and reacts with triphenylphosphine and DIAD. Compound 6 removes Ns protective group under the action of p-tert-butylthiophenol to obtain compound 7 with a yield of 88%. Subsequently, compound 8 is obtained under the action of TBAF. The synthetic route has 6 steps in total, and the total yield is 72%. The invention uses commercial reagents as raw materials, reduces reaction costs, and has relatively mild use conditions and simple experimental operations, and obtains amine compounds with a good yield, and at the same time lays a certain foundation for the synthesis of cephalotaxine. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 is the H NMR spectrum of compound 3 obtained in Example 1;
[0019] Figure 2 is the C NMR spectrum of compound 3 obtained in Example 1;
[0020] Figure 3 is the H NMR spectrum of compound 6 obtained in Example 1;
[0021] Figure 4 is the C NMR spectrum of compound 6 obtained in Example 1;
[0022] Figure 5 It is the H NMR spectrum of the amine compound obtained in Example 1. DETAILED DESCRIPTION
[0023] Specific implementation method 1: In this implementation method, a method for preparing an amine compound is carried out according to the following steps:
[0024] 1. Sinapic acid was subjected to Pd / C catalytic hydrogenation and Fischer esterification to obtain compound 2;
[0025] 2. Compound 2 and imidazole were added to a reaction bottle, dichloromethane was added under ice bath conditions, tert-butyldimethylsilyl chloride was added after dissolution, the temperature was raised to room temperature, the reaction was quenched after the reaction was complete, and then the organic solvent was removed by extraction and rotary evaporation, and the compound 3 was obtained after separation and purification;
[0026] 3. Compound 3 was added to a reaction tube, treated with anhydrous and oxygen-free conditions three times, then filled with nitrogen, and then dichloromethane was added, stirred to dissolve, and then continued to stir under ice bath conditions, and diisobutylaluminum hydride was added dropwise, and the reaction system was kept at 0°C. After the reaction was completed, a saturated sodium potassium tartrate solution and ethyl acetate were added and stirred until the reaction system was clear, and then extracted, and the organic solvent was removed by rotary evaporation, and separated and purified to obtain compound 4;
[0027] 4. At room temperature, piperidine reacts with p-nitrobenzenesulfonyl chloride and sodium carbonate in tetrahydrofuran solution to obtain compound 5;
[0028] 5. Compound 4, compound 5 and triphenylphosphine were added to the reaction tube, and nitrogen was filled after the anhydrous and oxygen-free treatment was completed. Xylene was added, and the mixture was placed in an ice bath and stirred. Diisopropyl azodicarboxylate was added dropwise. After the reaction was completed, the organic solvent was removed by rotary evaporation, and the mixture was separated and purified to obtain compound 6;
[0029] 6. Compound 6 and potassium carbonate were added to a glass bottle, and then DMF was added. After stirring and dissolving, p-methylthiophenol was added. After the reaction was completed, the reaction was quenched, and the organic phase was extracted and washed. The DMF solvent was removed by rotary evaporation, and then separated and purified to obtain compound 7;
[0030] 7. Add compound 7 to a reaction bottle, add a magnet (the magnet is used to stir the reaction) and tetrabutylammonium fluoride (TBAF), then add tetrahydrofuran, stir at room temperature, quench the reaction after the reaction is completed, extract, and remove the solvent by rotary evaporation of the organic phase. Separate and purify to obtain an amine compound.
[0031] Specific embodiment 2: This embodiment is different from specific embodiment 1 in that: the specific preparation method of compound 2 in step 1 is: add sinapinic acid and Pd / C to a reaction tube, evacuate and replace nitrogen three times, add methanol and chlorobenzene under nitrogen conditions, stir, monitor the reaction progress by TLC, after 48 hours of reaction, the solution changes from gray to black, and the raw materials are completely reacted, and methanol is evaporated by rotary evaporation to obtain a concentrated crude product, which is filtered on a silica gel column to obtain compound 2. The rest is the same as specific embodiment 1.
[0032] Specific implementation method 3: This implementation method is different from specific implementation method 1 or 2 in that dichloromethane is used for extraction in step 2. The rest is the same as specific implementation method 1 or 2.
[0033] Specific embodiment 4: This embodiment differs from specific embodiments 1 to 3 in that the anhydrous and oxygen-free treatment in step 3 and step 5 is to remove water and oxygen by heating at 400° C. with a drying gun under vacuum conditions. The rest is the same as specific embodiments 1 to 3.
[0034] Specific embodiment 5: This embodiment differs from specific embodiments 1 to 4 in that ethyl acetate is used for extraction in step 3. The rest is the same as specific embodiments 1 to 4.
[0035] Specific embodiment 6: This embodiment is different from specific embodiments 1 to 5 in that H2O is added in steps 2, 6 and 7 to quench the reaction. The rest is the same as specific embodiments 1 to 5.
[0036] Specific embodiment 7: This embodiment is different from specific embodiments 1 to 6 in that the temperature of the ice bath is 0° C. The rest is the same as specific embodiments 1 to 6.
[0037] Specific embodiment 8: This embodiment differs from specific embodiments 1 to 7 in that the separation and purification adopts silica gel column chromatography. The rest is the same as specific embodiments 1 to 7.
[0038] Specific embodiment 9: This embodiment is different from specific embodiments 1 to 8 in that: the specific preparation method of compound 5 in step 4 is: add piperonyl ethylamine and p-nitrobenzenesulfonyl chloride to a glass reaction bottle, add tetrahydrofuran and H2O, stir at room temperature for 3 hours, quench the reaction after the reaction is completed, extract, remove the obtained crude product solution by rotary evaporation, and separate the obtained crude product by column to obtain compound 5. The rest is the same as specific embodiments 1 to 8.
[0039] Specific embodiment 10: This embodiment differs from specific embodiments 1 to 9 in that: in the method for preparing compound 5, H2O is added to quench the reaction, and then ethyl acetate is used for extraction. The rest is the same as specific embodiments 1 to 9.
[0040] The content of the present invention is not limited to the content of the above-mentioned embodiments. The combination of one or several specific embodiments can also achieve the purpose of the invention.
[0041] Example 1: The preparation method of an amine compound in this example is carried out according to the following steps:
[0042] 1. Commercial reagents sinapinic acid 1 (2.2 g, 10 mmol) and Pd / C (0.2 mol%) were added to a 50 mL Schlenk tube, and the vacuum was replaced with nitrogen three times. Methanol (15 mL) and chlorobenzene (5 mol%) were added under nitrogen conditions. A balloon filled with hydrogen was inserted into the reaction tube and stirred. The reaction progress was monitored by TLC. After 48 hours of reaction, the solution changed from gray to black, indicating that the raw materials were completely reacted. Methanol was evaporated by rotary evaporation to obtain a concentrated crude product, which was filtered on a silica gel column to obtain compound 2 (2.3 g).
[0043]
[0044] Its NMR data analysis is: 1HNMR (400MHz, Chloroform-d) δ6.27 (s, 2H), 3.73 (s, 6H), 3.60 (s, 3H), 2.85 (t, J = 7.8 Hz, 2H), 2.53 (t, J = 7.8 Hz, 2H)
[0045] 2. Add compound 2 (1.2 g, 4.9 mmol) and imidazole (0.6 g, 8.8 mmol) to a 20 mL reaction bottle, then put it in an ice bath, add dichloromethane (5 mL), and after the compound is completely dissolved, add TBSCl (1.2 g, 7.5 mmol) to it, the solution turns white, and then slowly warms to room temperature. TLC monitors the reaction process. After about 7 hours, the reaction is complete, the solution is clear, and white solids precipitate. Post-treatment: Add H2O to the reaction bottle, stir until the solution is clear, then add dichloromethane to extract three times, rotary evaporation to remove the organic solvent, and use a silica gel column chromatography separation with a polarity of PE / EtOAc = 10:1 eluent to obtain the target product 3 (1.7 g, 4.9 mmol, 99%). It is a light yellow oily liquid.
[0046]
[0047] Figure 1 is the H NMR spectrum of compound 3; Figure 2 is the C NMR spectrum of compound 3;
[0048] Its NMR data analysis is: Compound 3:R f =0.5(silica gel,PE / EtOAc=10:1,UV,I2)
[0049] 1 H NMR (400MHz, Chloroform-d) δ6.36 (s, 2H), 3.76 (s, 6H), 3.67 (s, 3H), 2.87 (t, J = 7.8Hz, 2H), 2.69-2.44 (m, 2H), 1.00 (d, J = 1.0Hz, 9H), 0.11 (s, 6H).
[0050] 3. Add compound 3 (0.36 g, 1.0 mmol) to a 10 mL Schlenk reaction tube with a piston, treat it three times without water and oxygen, and then fill the system with nitrogen. Then add dichloromethane (10 mL) to it, stir to dissolve the compound, put it in an ice bath, and stir for another five minutes. Then, add diisobutylaluminum hydride (1.47 mL, 2.2 mmol) dropwise with a syringe. Bubbles are generated during this process, and the solution is colorless and transparent. Maintain the reaction system at 0 ° C, monitor the reaction progress by TLC, and the reaction is completed after about 2 hours. Add potassium sodium tartrate aqueous solution and ethyl acetate to the reaction tube and stir to neutralize the excess diisobutylaluminum hydride. A white solid appears, accelerate the stirring, wait until the solution is stirred until clear, and then extract it with ethyl acetate three times. Rotary evaporation removes the organic solvent to obtain a crude product, and then silica gel column chromatography is used to separate and purify the compound to obtain product 4 (0.3 g, 0.96 mmol, 96%). It is a colorless oily liquid.
[0051]
[0052] Its NMR data analysis is: Compound 4:R f =0.25(silica gel,PE / EtOAc=10:1,UV,I2)
[0053] 1 H NMR (400MHz, Chloroform-d) δ6.37(s,2H),3.77(s,6H),3.67(t,J=6.4Hz,2H),2.63(t,J=8.6,2H),1.94-1.82(m,2H),1.00(s,9H),0.11(s,6H).
[0054] 4. Add commercial reagents piperidine (0.8 g, 6 mmol) and p-nitrobenzenesulfonyl chloride (1.45 g, 6.6 mmol) into a 20 mL glass reaction bottle, add THF 10 mL, H2O 5 mL, stir at room temperature for 3 h, and after the reaction is completed, add H2O and ethyl acetate for extraction. The obtained crude product solution is removed by rotary evaporation, and the obtained crude product is separated by column to obtain compound 5 (1.9 g, 93%) as a yellow solid.
[0055] Its NMR data analysis is: 1H NMR (400MHz, Chloroform-d) δ8.49-8.17 (m, 2H), 7.96-7.89 (m, 2H), 6.70 (d, J = 7.8 Hz, 1H), 6.55-6.44 (m, 2H), 5.91 (s, 2H), 3.26 (t, J = 6.4 Hz, 2H), 2.70 (t, J = 6.6 Hz, 2H).
[0056]
[0057] 5. Add compound 4 (0.35g, 1.08mmol), 5 (0.67g, 1.9mmol), and triphenylphosphine (0.56g, 2.1mmol) to a 10mL Schlenk reaction tube with a piston. After the anhydrous and oxygen-free treatment is completed, nitrogen is filled into the system. Add xylene (1mL) to dissolve the compound, put it in an ice bath and stir for five minutes, and drop diisopropyl azodicarboxylate (0.45mL, 2.2mL) with a 500μL micro syringe. The solution turns black and gradually warms to room temperature. TLC monitors the reaction progress. After about 9h, the reaction is completed and the solution turns brown-black. After treatment, the solvent is removed by rotary evaporation. The crude product is separated and purified by silica gel column chromatography. The polarity of the eluent is PE / EtOAc=10:1~4:1, and the target product 6 (0.38g, 0.89mmol, 88%) is obtained as a dark yellow oily liquid.
[0058]
[0059] Figure 3 is the H NMR spectrum of compound 6; Figure 4 is the C NMR spectrum of compound 6;
[0060] Its NMR data analysis is: Compound 6:R f =0.5(silica gel,PE / EtOAc=4:1,UV)
[0061] 1 H NMR (400MHz, Chloroform-d) δ8.28(d,J=8.8Hz,2H),7.84(d,J=8.8Hz,2H),6.68(d,J=7.9Hz,1H),6.53(d,J=7.1Hz,2H),6.35(d,J=9.2Hz,2H),5.90( s,2H),3.78(s,3H),3.43-3.28(m,2H),3.24-3.16(m,2H),2.76-2.68(m,2 H), 2.54 (t, J = 7.2Hz, 2H), 1.87 (p, J = 7.3Hz, 2H), 1.01 (s, 9H), 0.12 (s, 6H).
[0062] VI. Compound 6 (13 mg, 0.02 mmol) and potassium carbonate (8 mg, 0.06 mmol) were added to a 4 mL glass bottle, and then DMF (0.1 mL) was added. After stirring and dissolving, p-methylthiophenol (4 μL, 0.02 mmol) was added with a micro syringe, and the solution turned brown-yellow. TLC monitored the reaction progress. The reaction was completed after about 5 h, and H2O was added to quench the reaction. Ethyl acetate was extracted three times, and the obtained organic phase was washed twice with saturated sodium chloride. The DMF solvent was removed by rotary evaporation to obtain a crude reaction product, which was separated and purified by column chromatography using eluents with polarity of PE / EtOAc = 1:1 to EA, CH2Cl2:MeOH = 10:1, to obtain the target product 7 (8 mg, 0.017 mmol, 88%) as a yellow solid.
[0063]
[0064] Its NMR data analysis is: Compound 7:R f =0.5(silica gel,CH2Cl2 / MeOH=10:1,UV,I2)
[0065] 1 H NMR(400MHz,Chloroform-d)δ6.85-6.55(m,3H),6.35(s,2H),5.91(s,2H),3.75(s,6H),3.00(s,4 H),2.90-2.79(m,2H),2.60(t,J=7.4Hz,2H),2.08(p,J=6.9,6.2Hz,2H),0.99(s,9H),0.10(s,6H).
[0066] 7. Compound 7 (13 mg, 0.02 mmol) was added to a 4 mL glass reaction bottle, a magnetic rod of appropriate size was added, TBAF (10 mg, 0.03 mmol) was weighed and added to the reaction bottle, THF was added with a syringe, and the mixture was stirred at room temperature. The reaction progress was monitored by TLC. After about 3 h, the reaction was completed, H2O was added, and ethyl acetate was extracted three times. The organic phase was removed by rotary evaporation, and the crude product was separated and purified by column chromatography using a silica gel column to obtain compound 8 (12 mg, 0.02 mmol, 100%), which was a brown oily liquid, i.e., an amine compound.
[0067]
[0068] Figure 5 is the H NMR spectrum of compound 8, and its NMR data analysis is: Compound 8: R f =0.25(silicagel,CH2Cl2 / MeOH=10:1,UV,I2)
[0069] 1 H NMR(400MHz,Chloroform-d)δ6.76-6.61(m,3H),6.45(s,2H),5.95(s,2H),3.87(s ,4H),3.11(s,2H),2.98-2.90(m,2H),2.66(t,J=7.4Hz,2H),2.22(h,J=7.7Hz,2H).
[0070] The invention uses commercial reagents as raw materials, reduces reaction costs, and has relatively mild use conditions and simple experimental operations. Amine compounds are obtained with a good yield, and a certain foundation is laid for the synthesis of cephalotaxine.
Claims
1. A method for preparing an amine compound, characterized in that The method is specifically carried out in the following steps:
1. Sinapic acid was subjected to Pd / C catalytic hydrogenation and Fischer esterification to obtain compound 2; 2. Compound 2 and imidazole were added to a reaction bottle, dichloromethane was added under ice bath conditions, tert-butyldimethylsilyl chloride was added after dissolution, the temperature was raised to room temperature, the reaction was quenched after the reaction was complete, and then the organic solvent was removed by extraction and rotary evaporation, and the compound 3 was obtained after separation and purification; 3. Compound 3 was added to a reaction tube, treated with anhydrous and oxygen-free conditions three times, then filled with nitrogen, and then dichloromethane was added, stirred to dissolve, and then continued to stir under ice bath conditions, and diisobutylaluminum hydride was added dropwise, and the reaction system was kept at 0°C. After the reaction was completed, a saturated sodium potassium tartrate solution and ethyl acetate were added and stirred until the reaction system was clear, and then extracted, and the organic solvent was removed by rotary evaporation, and separated and purified to obtain compound 4; 4. At room temperature, piperidine reacts with p-nitrobenzenesulfonyl chloride and sodium carbonate in tetrahydrofuran solution to obtain compound 5; 5. Compound 4, compound 5 and triphenylphosphine were added to the reaction tube, and nitrogen was filled after the anhydrous and oxygen-free treatment was completed. Xylene was added, and the mixture was placed in an ice bath and stirred. Diisopropyl azodicarboxylate was added dropwise. After the reaction was completed, the organic solvent was removed by rotary evaporation, and the mixture was separated and purified to obtain compound 6; 6. Compound 6 and potassium carbonate were added to a glass bottle, and then N,N-dimethylformamide was added. After stirring and dissolving, p-methylthiophenol was added. After the reaction was completed, the reaction was quenched, and the organic phase was extracted and washed. N,N-dimethylformamide was removed by rotary evaporation, and then separated and purified to obtain compound 7; 7. Add compound 7 to a reaction bottle, add tert-butyldimethylsilyl chloride, and then add tetrahydrofuran, stir at room temperature, quench the reaction after the reaction is completed, extract, and remove the solvent by rotary evaporation of the organic phase, separate and purify to obtain an amine compound.
2. The method for preparing an amine compound according to claim 1, characterized in that The specific preparation method of compound 2 in step 1 is: add sinapinic acid and Pd / C to a reaction tube, evacuate and replace with nitrogen three times, add methanol and chlorobenzene under nitrogen conditions, stir, monitor the reaction progress by TLC, after 48 hours of reaction, the solution changes from gray to black, and the raw materials are completely reacted, and methanol is rotary evaporated to obtain a concentrated crude product, which is filtered on a silica gel column to obtain compound 2.
3. The method for preparing an amine compound according to claim 1, characterized in that Step 2: Extraction with dichloromethane.
4. The method for preparing an amine compound according to claim 1, characterized in that The anhydrous and oxygen-free treatment in step 3 and step 5 is to remove water and oxygen by heating at 400° C. with a drying gun under vacuum conditions.
5. The method for preparing an amine compound according to claim 4, characterized in that Step three: extracting with ethyl acetate.
6. The method for preparing an amine compound according to claim 1, characterized in that In steps 2, 6 and 7, H2O was added to quench the reaction.
7. The method for preparing an amine compound according to claim 1, characterized in that The ice bath temperature was 0°C.
8. The method for preparing an amine compound according to claim 1, characterized in that The separation and purification adopts silica gel column chromatography.
9. The method for preparing an amine compound according to claim 1, characterized in that The specific preparation method of compound 5 in step 4 is: add piperidine and p-nitrobenzenesulfonyl chloride into a glass reaction bottle, add tetrahydrofuran and H2O, stir at room temperature for 3 hours, quench the reaction after the reaction is completed, extract, remove the obtained crude product solution by rotary evaporation, and separate the obtained crude product by column to obtain compound 5.
10. The method for preparing an amine compound according to claim 9, characterized in that In the method for preparing compound 5, H2O was added to quench the reaction, followed by extraction with ethyl acetate.