A pyrrolin-2(3H)-one compound, its preparation method and use

Abstract

A compound of the formula LW pyrrolin-2(3H)-one, with the following structural formula: In the formula, R 1 is a group selected from the following: alkyl, arylmethyl, R 2 is a group selected from the following: alkyl, aryl, heteroaryl, R 3 is a group selected from the following: cyano, carboxylate, acyl; its preparation method is obtained by reacting 2-bromoacetamide with acylacetonitrile or acyl acetate or acyl ketone, etc. by a "one-pot" reaction under certain conditions; this method has mild reaction conditions, inexpensive reagents, is easy to operate, can conveniently prepare polysubstituted pyrrolin-2-one compounds, and can be used as a synthetic precursor for other heterocyclic compounds.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and specifically discloses a pyrrolin-2(3H)-one compound (LW) and its preparation method and use. Background Art

[0002] The pyrrolin-2-one skeleton exists in compounds with important biological activities and functions. For example, compounds containing this type of structure have the effect of treating metabolic disease Niemann–Pick disease type C (Helquist, P. et al. J. Med. Chem. 2009, 52, 6494–6498). Some compounds containing this structural unit have activities such as anti-tumor, antibacterial, and antioxidant activities (Dallavalle, S. et al. ChemMedChem 2016, 11, 1–6; Olgen, S. et al. Naturforsch. C 2009, 64, 155–162). This type of skeleton compound has been found to have plant protection effects (Oliver, W. et al. 1999, WO 9950243 A1 19991007). In addition, this type of skeleton also exists in the composition of inks and dyes, and has advantages such as good anti-aggregation, low initial viscosity, and easy storage (Takashi, Y. JP 2017203102; JP 2017171720). On the other hand, this skeleton compound is further applied as an important synthetic intermediate in the synthesis of other functional compounds in organic synthesis (Gallagher, T. et al. Org. Lett. 2016, 18, 4124-4127; Zhang, W. B. et al. Org. Lett. 2017, 19, 1144-1147). In view of the diverse activities and functions of this type of compound, developing a simple synthetic method for compounds containing this skeleton structure has important theoretical and practical application values. Summary of the Invention

[0003] In order to overcome the above problems of the prior art, in the first aspect of the present invention, it is intended to provide a pyrrolin-2(3H)-one compound (LW) with important biological activities and functions:

[0004]

[0005] Wherein, R 1 is a group selected from the following: alkyl, arylmethyl, and the alkyl is C1-C 18 alkyl or cycloalkyl, and the arylmethyl is benzyl or heteroaryl-methyl;

[0006] R 2 is a group selected from the following: alkyl, aryl, heteroaryl;

[0007] R 3 is a group selected from the following: cyano group, carboxylic acid ester group, acyl group.

[0008] Preferably, the pyrrolin-2(3H)-one compound is selected from:

[0009]

[0010] The second object of the present invention is to provide a preparation method of the compound of the present invention, and pyrrolin-2-one compounds are synthesized by reacting bromoacetamide with acylacetonitrile or acyl acetate or 1,3-diketocarbonyl compounds.

[0011] Specifically, the preparation method of the pyrrolin-2(3H)-one compound includes the following steps:

[0012] (1) At a certain temperature, in an inert solvent and in the presence of a catalyst, compound A reacts with compound B for 1-96 hours, filter to remove solids. Rotate evaporate the filtrate to remove the solvent, and directly proceed to the following reaction without further purification.

[0013] (2) Concentrate the above solution at a certain temperature, in an inert solvent and in the presence of an acidic catalyst, react for 1-12 hours, rotate evaporate to remove the solvent, and the crude product is purified by column chromatography to obtain pyrrolin-2(2H)-one of formula LW;

[0014] The reaction formula is as follows

[0015]

[0016] Wherein, R1 is selected from the following groups: the alkyl group is preferably a C1-C18 alkyl group or a cycloalkyl group, and the arylmethyl group is preferably a benzyl group or a heteroaryl methyl group.

[0017] Wherein, R2 is a group selected from the following: alkyl group, aryl group, heteroaryl group,

[0018] Wherein, R3 is a group selected from the following: -CN, carboxylic acid ester group, acyl group.

[0019] In the above preparation method, preferably, in step (1), the molar ratio of the compound of formula A to the compound of B is 0.6:1 to 1:10.

[0020] In the above preparation method, the catalyst in step (1) is an organic base or an inorganic base. The organic bases are triethylamine, pyridine, piperidine, diethylamine, dimethylamine, and the inorganic bases are sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide; the preferred catalysts are K2CO3 or sodium methoxide; the solvents are dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran, acetone, toluene, xylene, diphenyl ether or dimethylformamide, and the preferred solvent is tetrahydrofuran. The molar ratio of bromoacetamide to the basic catalyst is 1:1 to 1:100; the reaction temperature is -40 to 100 °C, preferably 0 to 40 °C, and the reaction time is 1 to 96 hours.

[0021] In the above preparation method, in the dehydration reaction of step (2), the acids used are hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, benzenesulfonic acid, p-toluenesulfonic acid, and the preferred one is p-toluenesulfonic acid. The molar ratio of bromoacetamide A to the acid catalyst is 1:0.1 to 1:10. The reaction solvent is tetrahydrofuran, acetone, toluene, xylene, dichloromethane, trichloromethane, carbon tetrachloride or dimethylformamide, and the preferred one is chloroform; the dehydration reaction temperature is -40 to 100 °C, preferably 0 to 40 °C; the dehydration reaction time is 1 to 12 hours.

[0022] In the preparation method of the compound of the present invention, the bromoacetamide compound of formula A can be commercially obtained, that is, from commercially available products, or the bromoacetamide compound can be obtained from the methods reported in the literature (Zhou, J.; Chen, Y.-J. et al J. Org. Chem. 2019, 84, 9179-9187; Lei, X.Q.; Shi, J.G. et al. Org. Lett. 2022, 24, 2837-2841.).

[0023] In some specific embodiments, the bromoacetamide compound A can be prepared by a synthesis method including the following steps according to Reaction Scheme 2.

[0024] In the above embodiments, the acylacetonitrile or acyl acetate or acyl ketone compound B are all commercially obtained, that is, from commercially available products.

[0025] The third object of the present invention is that the pyrrolin-2-one compound of the present invention can be conveniently converted into other pyrrole compounds. For example, in the following Reaction Schemes Eq.1, Eq.2, Eq.3, Eq.4, according to relevant literature reports, LW-1 can be converted into other pyrrolinones or pyrroles or other heterocyclic compounds:

[0026]

[0027] In the present invention, unless otherwise specified, the terms or words used in the specification and claims have the conventional meanings known to those skilled in the art.

[0028] In the present invention, unless otherwise specified, the reaction vessels, devices, reaction conditions, etc. not specifically mentioned in the specification and claims are conventional in the art.

[0029] Compared with the prior art, the present invention has the following advantages:

[0030] The present invention prepares pyrrolidin-2-one compounds (LW series) with rich biological activities.

[0031] The preparation method of pyrrolidin-2-one in the present invention has mild conditions, low reagent cost, strong operability, and the reaction yield is over 70% in most cases, up to 94% at the highest. Moreover, the pyrrolidin-2-one compound LW obtained by the preparation method of the present invention can be used as a synthetic precursor of pyrrole compounds with important biological activities and medicinal values. Detailed implementation manners

[0032] The technical solutions of the present invention will be further clearly and completely described below in conjunction with the detailed implementation manners. It should be understood that the implementation manners herein are only used to explain the present invention and cannot be construed as limiting the protection scope of the present invention.

[0033] General synthesis method

[0034] The compounds of the present invention can be prepared using the following general synthesis method and the methods described in detail in the examples. The reaction conditions involved are illustrative rather than restrictive, and those skilled in the art can also make conventional adjustments to the reaction conditions according to the method steps described in this application and prepare them in a similar manner.

[0035] At 0 °C, in a tetrahydrofuran solvent, in the presence of an appropriate amount of K2CO3 or NaOCH3, the compound of formula A is reacted with B for 12 - 48 hours; the solid is filtered off, the filtrate is concentrated, and the residue is directly added to chloroform as a solvent and an appropriate amount of p-toluenesulfonic acid without further purification. The reaction solution is reacted at 40 °C for 1 - 10 hours, and the reaction is monitored by TLC until completion. The pyrrolidin-2-one product LW is obtained by column chromatography, and the yield reaches up to 94%.

[0036] The synthesis method of the pyrrolidin-2-one compounds of the present invention is shown in Reaction Scheme 1.

[0037]

[0038] Preferably, the synthesis of bromoacetamide compound A

[0039]

[0040] Dissolve the corresponding alcohol I (1 equiv), N-hydroxyphthalimide II (1.3 equiv), and triphenylphosphine (1.5 equiv) in anhydrous tetrahydrofuran and cool to 0 °C. While stirring continuously, slowly drip a solution of diisopropyl azodicarboxylate (DIAD) (1.5 equiv) in anhydrous tetrahydrofuran into the previous reaction system. After the addition is complete, raise the temperature to room temperature and continue the reaction for 4 hours. Monitor the reaction by TLC until it is complete. Rotate evaporate to remove the solvent, and subject the residue to column chromatography (petroleum ether - ethyl acetate system) to obtain white solid III for the next reaction.

[0041] Dissolve N-alkoxyphthalimide III (1 equiv) in a mixed solvent of methanol / dichloromethane (1:2), slowly drip hydrazine hydrate (2 equiv), and react at room temperature for 2 hours. Monitor the reaction by TLC until it is complete. Rotate evaporate to remove the solvent, wash the residual solid with dichloromethane, collect and concentrate the filtrate to obtain the crude product of alkylhydroxylamine, which is directly used for the next step without purification.

[0042] Dissolve potassium carbonate (2 equiv) in a mixed solvent of ethyl acetate / water (1:2), add the freshly prepared crude product of alkylhydroxylamine III (1 equiv), and cool the system to 0 °C. Dissolve bromoacetyl bromide (1.2 equiv) in a small amount of ethyl acetate and slowly drip it in, and stir at room temperature for 1 hour. After the reaction is complete, separate the aqueous phase, extract with ethyl acetate twice, combine the organic phases, dry over anhydrous sodium sulfate, remove the solvent under reduced pressure, and perform column chromatography using a petroleum ether / ethyl acetate system to obtain the bromoamide substrate A.

[0043] According to the above general synthesis method, the pyrrolidin-2-one compounds of this application were synthesized. The specific structures are shown in Table 1 below, and the corresponding hydrogen spectrum data of the compounds are shown in Table 2 below:

[0044]

[0045] Table 1 Data Sheet of the Synthesized Pyrrolidin-2-one Compound LW

[0046]

[0047]

[0048]

[0049] Note: An oil-like substance means that the substance is in an oil-like state at room temperature.

[0050] Table 2 Corresponding Hydrogen Spectrum Data Sheet of the Synthesized Pyrrolidin-2-one Compound LW

[0051]

[0052]

[0053] The following several representative compounds were selected and their preparation methods were described in more detail:

[0054] Example 1 LW-1: Synthesis of 4-cyano-1-benzyloxy-5-phenyl-pyrrolin-2(3H)-one

[0055] Bromoacetamide A1 (73.2 mg, 0.3 mmol), benzoylacetonitrile B1 (36.3 mg, 0.25 mmol), sodium methoxide (0.6 mmol, 32.4 mg) and sodium iodide (0.04 mmol, 6 mg) were added to a 10 mL round-bottom flask. 2 mL of anhydrous tetrahydrofuran was added, and the mixture was stirred at room temperature for 12 hours. The reaction of B1 was monitored by TLC until completion. The mixture was filtered, and the solvent was removed by rotary evaporation. The residue was dissolved in 2 mL of chloroform, and p-toluenesulfonic acid (0.1 mmol, 17.2 mg) was added. The reaction was carried out at 40 °C for 10 hours, and the solvent was removed by rotary evaporation. The product was separated by column chromatography (eluent: petroleum ether: ethyl acetate, 5:1, v / v) to obtain 67 mg of a white solid with a yield of 92%. Mp: 137-139 °C. 1 H NMR (500 MHz, CDCl3): δ 7.57–7.50 (m, 3H), 7.48–7.43 (m, 2H), 7.32–7.27 (m, 1H), 7.23–7.18 (m, 2H), 7.06–7.01 (m, 2H), 4.89 (s, 2H), 3.38 (s, 2H). 13 C NMR (126 MHz, CDCl3): δ 169.1, 156.6, 132.4, 131.5, 130.0, 129.4, 128.7, 128.6, 128.5, 125.6, 115.5, 79.5, 78.8, 35.3. HRMS ESI Calcdfor C 18 H 14 N2NaO2 [M+Na] + : 313.0947, Found: 313.0948.

[0056] Example 2 LW-11: Synthesis of 4-cyano-1-benzyloxy-5-methyl-pyrrolin-2(3H)-one

[0057] Add bromoacetamide A1 (73.2 mg, 0.3 mmol), acetoacetonitrile (20.7 mg, 0.25 mmol), sodium ethoxide (0.6 mmol, 40.8 mg) into a 10 mL round-bottom flask, add 2 mL of anhydrous tetrahydrofuran, stir at room temperature for 12 hours, and monitor by TLC until acetoacetonitrile is completely consumed. Filter, rotary evaporate the solvent from the filtrate, add 5 mL of chloroform to dissolve, add p-toluenesulfonic acid (0.1 mmol, 17.2 mg), react at 40 °C for 4 hours, rotary evaporate the solvent, and the residue is purified by column chromatography (eluent: petroleum ether: ethyl acetate, 4:1, v / v) to obtain 46 mg of white solid, with a yield of 81%. m.p. 109 - 110 °C. 1 H NMR (500 MHz, CDCl3) δ 7.46–7.34 (m, 5H), 5.09 (s, 2H), 3.21 (q, J=2.4 Hz, 2H), 1.87 (t, J=2.4 Hz, 3H); 13 C NMR (126 MHz, CDCl3) δ 169.5, 157.0, 133.4, 130.1, 129.8, 128.9, 114.8, 79.2, 79.1, 34.8, 11.9; HRMS ESI Calcd for C 13 H 12 N2NaO2 [M+Na] + : 251.0791, Found: 251.0791.

[0058] Example 3 LW-13: Synthesis of ethyl 4-carboxylate-1-benzyloxy-5-methyl-pyrrolin-2(3H)-one

[0059] Add bromoacetamide A1 (49 mg, 0.2 mmol), ethyl acetoacetate (33.8 mg, 0.26 mmol), potassium carbonate (0.6 mmol, 82.8 mg) and sodium iodide (0.04 mmol, 6 mg) into a 10 mL round-bottom flask, add 1 mL of anhydrous tetrahydrofuran, stir at room temperature for 48 hours, and monitor by TLC until bromoacetamide A1 completely reacts. Filter, rotary evaporate the solvent from the filtrate, add 2 mL of chloroform to dissolve, add p-toluenesulfonic acid (0.5 mmol, 86 mg), react at 40 °C for 1 hour, rotary evaporate the solvent, and purify by column chromatography (eluent: petroleum ether: ethyl acetate, 5:1, v / v) to obtain 45 mg of white solid, with a yield of 82%. Mp: 44 - 46 °C. 11H NMR (500 MHz, CDCl3): δ 7.48–7.35 (m, 5H), 5.10 (s, 2H), 4.18 (q, J = 7.1 Hz, 2H), 3.24 (q, J = 2.4 Hz, 2H), 2.14 (t, J = 2.4 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H). 13 13C NMR (126 MHz, CDCl3): δ 170.9, 163.7, 153.2, 133.7, 130.0, 129.5, 128.7, 99.6, 78.9, 59.9, 34.5, 14.3, 11.0. HRMSESI Calcd for C 15 H 17 NNaO4 [M+Na] + : 298.1050, Found: 298.1050。

[0060] Example 4 LW-15: Synthesis of 4-Acetyl-1-benzyloxy-5-methyl-pyrrolin-2(3H)-one Bromoamide A1 (73.2 mg, 0.3 mmol), 2,4-pentanedione (25 mg, 0.25 mmol), and potassium carbonate (0.6 mmol, 82.8 mg) were added to a 10 mL round-bottom flask. 2 mL of anhydrous tetrahydrofuran was added, and the mixture was stirred at room temperature for 12 hours. The reaction of 2,4-pentanedione was monitored by TLC until completion. The mixture was filtered, and the solvent was removed by rotary evaporation. The residue was dissolved in 2 mL of chloroform, and p-toluenesulfonic acid (0.1 mmol, 17.2 mg) was added. The reaction was carried out at 0 °C for 10 hours, and the solvent was removed by rotary evaporation. Column chromatography (eluent: petroleum ether:ethyl acetate, 3:1, v / v) gave 44 mg of a white solid with a yield of 72%. Mp: 106-108 °C. 1 1H NMR (500 MHz, CDCl3): δ 7.45–7.36 (m, 5H), 5.11 (s, 2H), 3.29 (q, J = 2.4 Hz, 2H), 2.19 (s, 3H), 2.16 (t, J = 2.3 Hz, 3H); 13 13C NMR (126 MHz, CDCl3): δ 192.3, 170.4, 152.6, 133.6, 130.0, 129.6, 128.8, 108.4, 79.0, 34.9, 29.0, 11.6. HRMS ESI Calcd for C 14 H 15 NNaO3 [M+Na] + : 268.0944, Found: 268.0945。

[0061] Example 5 LW-16: Synthesis of 4-Cyano-1-methoxy-5-methyl-pyrrolin-2(3H)-one

[0062] In a 10 mL round-bottom flask, bromoacetamide A16 (50.1 mg, 0.3 mmol), benzoylacetonitrile B1 (36.3 mg, 0.25 mmol), sodium methoxide (0.6 mmol, 32.4 mg), and sodium iodide (0.04 mmol, 6 mg) were added. 2 mL of anhydrous tetrahydrofuran was added, and the mixture was stirred at room temperature for 96 hours. The reaction of B1 was monitored by TLC until completion. The mixture was filtered, and the solvent was removed by rotary evaporation of the filtrate. 2 mL of chloroform was added to dissolve the residue, and p-toluenesulfonic acid (0.1 mmol, 17.2 mg) was added. The reaction was carried out at 40 °C for 10 hours, and the solvent was removed by rotary evaporation. Column chromatography (eluent: petroleum ether:ethyl acetate, 5:1, v / v) gave 45 mg of a white solid with a yield of 84%. mp 45 - 47 °C; 1 H NMR (500 MHz, CDCl3) δ 7.74 (d, J = 7.2 Hz, 2H), 7.62–7.49 (m, 3H), 3.74 (s, 3H), 3.40 (s, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.26, 155.68, 131.79, 129.00, 128.31, 125.40, 115.39, 80.12, 64.67, 35.35. HRMS Calcd. For C 12 H 10 N2NaO2 + : 237.0634, found: 237.0634。

[0063] Example 6 LW-19: Synthesis of 4-cyano-1-dodecyloxy-5-methyl-pyrrolin-2(3H)-one

[0064] In a 10 mL round-bottom flask, bromoacetamide A19 (96.6 mg, 0.3 mmol), benzoylacetonitrile B1 (36.3 mg, 0.25 mmol), sodium methoxide (0.6 mmol, 32.4 mg), and sodium iodide (0.04 mmol, 6 mg) were added. 2 mL of anhydrous tetrahydrofuran was added, and the mixture was stirred at room temperature for 96 hours. The reaction of B1 was monitored by TLC until completion. The mixture was filtered, and the solvent was removed by rotary evaporation of the filtrate. 2 mL of chloroform was added to dissolve the residue, and p-toluenesulfonic acid (2.0 mmol, 344 mg) was added. The reaction was carried out at room temperature for 12 hours, and the solvent was removed by rotary evaporation. Column chromatography (eluent: petroleum ether:ethyl acetate, 5:1, v / v) gave 71.8 mg of a white solid with a yield of 78%, mp 68 - 70 °C. 11H NMR (500 MHz, CDCl3) δ 7.76–7.68 (m, 2H), 7.59–7.47 (m, 3H), 3.85 (t, J = 6.5 Hz, 2H), 3.38 (s, 2H), 1.53–1.44 (m, 2H), 1.33–1.05 (m, 18H), 0.88 (t, J = 7.0 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ 169.19, 156.23, 131.69, 128.86, 128.49, 125.57, 115.50, 79.83, 77.58, 35.36, 31.85, 29.55, 29.42, 29.29, 29.28, 29.02, 27.64, 25.41, 22.63, 14.07. HRMS Calcd. For C 23 H 32 N2NaO2 [M+Na] + : 391.2356, found: 391.2357。

[0065] Example 7 LW-20: Synthesis of 4-Cyano-1-cyclohexyloxy-5-methyl-pyrrolidin-2(3H)-one

[0066] Add bromoacetamide A20 (74.7 mg, 0.3 mmol), benzoylacetonitrile B1 (36.3 mg, 0.25 mmol), sodium methoxide (0.6 mmol, 32.4 mg) and sodium iodide (0.04 mmol, 6 mg) into a 10 mL round-bottom flask. Add 2 mL of anhydrous tetrahydrofuran and stir at room temperature for 72 hours. Monitor the reaction of B1 by TLC until it is complete. Filter, rotary evaporate the solvent from the filtrate, add 2 mL of chloroform to dissolve, add p-toluenesulfonic acid (0.3 mmol, 51.6 mg), react at 40 °C for 1 hour, rotary evaporate the solvent, and perform column chromatography (eluent petroleum ether: ethyl acetate, 4:1, v / v) to obtain 60 mg of white solid with a yield of 85%. mp 92 - 94 °C. 1 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 7.2 Hz, 2H), 7.51–7.40 (m, 3H), 3.78 (d, J = 3.9 Hz, 1H), 3.33 (s, 2H), 1.66 (d, J = 10.3 Hz, 2H), 1.54 (d, J = 6.8 Hz, 2H), 1.39–1.30 (m, 1H), 1.11–0.94 (m, 5H). 1313C NMR (126 MHz, CDCl3) δ 169.36, 156.98, 131.48, 128.73, 128.64, 126.04, 115.57, 85.46, 79.66, 35.27, 30.36, 24.90, 23.48. HRMS Calcd. For C 17 H 18 N2NaO2 [M+Na] + : 305.1260, found: 305.1257。

[0067] Example 8 LW-21: Synthesis of 4-Cyano-1-cyclododecyloxy-5-methyl-pyrrolin-2(3H)-one

[0068] Add bromoacetamide A21 (95.7 mg, 0.3 mmol), benzoylacetonitrile B1 (36.3 mg, 0.25 mmol), sodium ethoxide (0.6 mmol, 32.4 mg) and sodium iodide (0.04 mmol, 6 mg) into a 10 mL round-bottom flask. Add 2 mL of anhydrous tetrahydrofuran and stir at room temperature for 12 hours. Monitor the reaction of B1 by TLC until it is complete. Filter, rotary evaporate the filtrate to remove the solvent, add 2 mL of chloroform to dissolve, add p-toluenesulfonic acid (1.0 mmol, 172 mg), react at room temperature for 10 hours, rotary evaporate to remove the solvent, and perform column chromatography (eluent: petroleum ether: ethyl acetate, 5:1, v / v) to obtain 66.7 mg of white solid with a yield of 73%. mp 88 - 90 °C 1 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J = 7.5 Hz, 2H), 7.46 (dt, J = 14.4, 7.1 Hz, 3H), 3.95 (t, J = 4.5 Hz, 1H), 3.33 (s, 2H), 1.37 (dt, J = 13.6, 6.9 Hz, 2H), 1.31 (dd, J = 11.5, 6.4 Hz, 2H), 1.21–1.08 (m, 15H), 1.00 (d, J = 6.0 Hz, 2H). 13 13C NMR (126 MHz, CDCl3) δ 169.45, 157.21, 131.45, 128.77, 128.65, 126.11, 115.50, 85.50, 79.87, 35.29, 27.90, 24.05, 23.39, 23.25, 23.06, 20.74. HRMS Calcd. For C 23 H 30 N2NaO2 [M+Na] + : 389.2199, found: 389.2199。

[0069] Other embodiments of the present disclosure will be readily apparent to those skilled in the art upon consideration of the specification and practice of the disclosure herein. This application is intended to cover any variations, uses, or adaptations of the present disclosure that follow the general principles of the present disclosure and include known common general knowledge or conventional technical means in the technical field not disclosed by the present disclosure. The specification and examples are only to be considered as exemplary, and the true scope and spirit of the present disclosure are pointed out by the claims of this application.

Claims

1. A method for preparing a pyrrolin-2(3H)-one compound, comprising the steps: (1) At a certain temperature, in an inert solvent, in the presence of a basic catalyst, react compound A with compound B for 1 - 96 hours, filter, remove the solid, rotary evaporate the filtrate to remove the solvent, and directly proceed to the following reaction without further purification; (2) At a certain temperature, in an inert solvent, in the presence of an acidic catalyst, react the above concentrated solution for 1 - 12 hours, rotary evaporate to remove the solvent, and purify the crude product by column chromatography to obtain a pyrrolin-2(3H)-one compound of formula LW; The basic catalyst in step (1) is an organic base or an inorganic base. The organic base is triethylamine, pyridine, piperidine, diethylamine or dimethylamine, and the inorganic base is sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, potassium ethoxide or potassium tert-butoxide; the molar ratio of compound A to the basic catalyst is 1:1 to 1:100; The acidic catalyst in step (2) is hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, benzenesulfonic acid or p-toluenesulfonic acid, and the molar ratio of compound A to the acidic catalyst is 1:0.1 to 1:10; The reaction formula is as follows: Among them, The pyrrolin-2(3H)-one compound of formula LW is selected from:

2. The method for preparing a pyrrolin-2(3H)-one compound according to claim 1, wherein in step (1), the molar ratio of compound A to compound B is 0.6:1 to 1:

10.

3. The method for preparing a pyrrolin-2(3H)-one compound according to claim 1 or 2, wherein: In step (1), the reaction solvent is tetrahydrofuran, acetone, toluene, xylene, dichloromethane, chloroform or carbon tetrachloride; the reaction temperature is -40 to 100 °C, and the reaction time is 1 - 96 hours; In step (2), the reaction solvent is tetrahydrofuran, acetone, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride or dimethylformamide; the reaction temperature is -40 to 100 °C; the reaction time is 1 - 12 hours.

4. The method for preparing a pyrrolin-2(3H)-one compound according to claim 3, wherein in step (1), the basic catalyst is potassium carbonate or sodium methoxide, the reaction temperature is 0 to 40 °C, and the reaction solvent is tetrahydrofuran; in step (2), the acidic catalyst is p-toluenesulfonic acid, the reaction solvent is chloroform, the reaction temperature is 0 to 40 °C, and the reaction time is 1 - 12 hours.

5. The method for preparing a pyrrolin-2(3H)-one compound according to claim 1, wherein in step (1), an auxiliary reagent LiI, NaI, KI, LiBr, NaBr or KBr is added, and the molar ratio of the auxiliary reagent to compound A is 0.01:1 - 100:

1.

6. The method for preparing a pyrrolin-2(3H)-one compound according to claim 5, wherein in step (1), the added auxiliary reagent is NaI.

7. A method for preparing a pyrrolin-2(3H)-one compound according to claim 1, wherein the pyrrolin-2(3H)-one compound can be converted into a pyrrole compound of Reaction Schemes Eq.1, Eq.2, Eq.3 or Eq.4:

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