CN105859630B - A kind of synthetic method and application of imidazolone derivatives - Google Patents

Abstract

The invention provides a synthesis method and application of imidazolone derivatives. The 2-amino group or imino group is prepared by using carbodiimide, hydrochloride of amino acid ester, tertiary amine and catalytic zinc trifluoromethanesulfonate. Substituted imidazolone derivatives. The synthetic method is scientific and reasonable, provides a general method for synthesizing imidazolone derivatives with various substituents, and can further synthesize more complex nitrogen heterocyclic molecules, such as benzimidazoimidazolones and the like. The method has easily available raw materials, wide application range, high separation yield, simple experimental equipment and operation, and is convenient for further development and application. The synthesized product has potential application value in biology, pharmacy, and materials.

Description

A kind of synthetic method and application of imidazolone derivative

technical field

The invention belongs to the field of medicinal chemistry, and relates to a series of nitrogen-containing heterocyclic compounds, especially a synthesis method and application of imidazolone derivatives.

Background technique

Guanidine compounds exist widely in living organisms. For example, the essential amino acid arginine in the human body contains guanidine groups, and many nitrogen-containing heterocyclic compounds also have guanidine groups, such as 2-aminoimidazolone derivatives. These molecules are used in a wide range of fields such as chemistry, biology, pharmaceuticals, and materials engineering.

As described below, the use of 2-aminoimidazolone compounds in various fields has been reported.

"The Structure of Dibromoagelaspongin-A Novel Bromine-ContainingGuani dine Derivative From the Marine Sponge Agelas sp. Tetrahedron 1989, 45, 3487", "Leucettines, a Class of Potent Inhibitors of cdc2-Like Kinases and DualSpecificity, Tyrosine Phosphorylation Regulated Kinases Derived from theMarine Sponge Leucettamine B:Modulation of Alternative Pre-RNASplicing.J.Med.Chem.2011,54,4172.” both recorded a series of natural molecules extracted from aquatic sponges, such as natural molecules Leucettines containing 2-aminoimidazole The structure of ketone, such molecules have a certain kinase inhibitory effect. "In Vitro Metabolism of a Thrombin Inhibitor and Quantitation of Metabolically Generated Cyanide. J. Pharmaceut. Biomed. 2005, 39, 1014." describes the inhibition of thrombin in vitro by polysubstituted 2-aminoimidazolones. "Preparation of Tricyclic Compounds as CRF Receptor Antagonists U.S.Pat.Appl.Publ.2009 US 20090186879 A1 20090723." records that polycyclic 2-aminoimidazolone compounds have antagonistic effects on some active enzymes. "Synthesis of Condensed Tetrahydroimidazo[1,2-a]quinazoline-1,5-dioneDerivatives. Tetrahedron 2012, 68, 3098." records that azaquinolinone imidazolone compounds have the potential to be used in biology and medicine.

The synthetic methods of such nitrogen-containing heterocyclic compounds provided by the current domestic and foreign literature all have their limitations. For example, the raw materials are complex and difficult to obtain, the reaction time is long, the yield is low, and the functional group tolerance is not good.

SUMMARY OF THE INVENTION

The invention provides an imidazolone derivative, especially a synthesis method and application of an imidazolone derivative whose 2-position is substituted by an amino group or an imino group.

The synthetic method starts from cheap and easily available general chemical raw materials to synthesize carbodiimide, amino acid ester, etc., and has low cost and high efficiency, and has great advantages compared with the existing method.

The synthetic method of imidazolone derivative of the present invention comprises the following steps:

A) the hydrochloride of amino acid ester shown in formula I, and zinc trifluoromethanesulfonate and tertiary amine are added in organic solvent to dissolve;

b) adding carbodiimide represented by formula II to the reaction solution of step a), and stirring the reaction at 50-100° C. for 4-10 hours;

c) post-processing the reaction solution of step b) to obtain the 2-aminoimidazolone shown in formula III, or the 2-iminoimidazolone shown in formula IV;

The basic reaction formula of the above reaction process is as follows:

or

in,

R ¹ and R ² are the same or different, and represent respectively a substituted or unsubstituted C _1-12 hydrocarbon group, a substituted or unsubstituted C _6-12 aryl group, an unsubstituted C _3-7 heterocyclic group, or a Substituted C _3-7 heterocyclyl;

R ³ and R ⁴ are the same or different, and are substituted or unsubstituted C _1-12 hydrocarbyl, substituted or unsubstituted C _1-12 alkoxy, substituted or unsubstituted C _2-12 alkoxycarbonyl, substituted or unsubstituted C 1-12 alkoxycarbonyl, substituted or unsubstituted C 1-12 alkoxy unsubstituted C _6-12 aryl, unsubstituted C _3-7 heterocyclyl or C _3-7 heterocyclyl substituted on a heterocycle;

The above-mentioned substituents are selected from functional groups such as hydrogen atom, hydroxyl, alkoxy, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester or amide;

R' ₃ N is a tertiary amine.

Preferably, R ¹ is alkyl, benzyl, or substituted phenyl, pyridine, pyrrole and other heterocyclic groups, R ² is alkyl, benzyl, or substituted phenyl, pyridine, pyrrole and other heterocyclic groups, R ³ is substituted alkyl, benzyl, or substituted phenyl, etc., R ⁴ is substituted alkyl, benzyl, or substituted pyridine, pyrrole and other heterocyclic groups.

The above-mentioned substituents include functional groups such as hydrogen atoms, hydroxyl groups, alkoxy groups, and halogens;

The synthetic method of the present invention can be carried out in air.

As for the organic solvent used in the synthesis method, it includes benzene, toluene or tetrahydrofuran, preferably anhydrous benzene.

In the synthesis method of the present invention, step a) can be dissolved at room temperature. The room temperature is preferably 25°C, and may fluctuate by 5°C, that is, 20-30°C.

The tertiary amine in step a) is preferably triethylamine or 4-(N,N'-dimethylamino)pyridine.

Step b) is preferably reacted at 80° C. for 8 h. In this step, an oil bath (eg, silicone oil, paraffin oil, etc.) or other heating methods can be used, as long as the reaction temperature is maintained at about 80°C.

The preferred range of the molar ratio of various reaction raw materials or reagents of the present invention is shown in Table 1:

Table 1. Preferred molar ratios of various reaction starting materials or reagents

The method of the present invention has no particular limitation on the ratio of the carbodiimide compound to the organic solvent, as long as the reaction solution can be stirred uniformly, preferably 1 mmol of the carbodiimide compound is dissolved in an organic solvent with a volume greater than 3 mL.

The zinc trifluoromethanesulfonate of the present invention can combine with amino acid ester to play an activation effect. Therefore, the added molar equivalents of the hydrochloride salt of the amino acid ester and the tertiary amine should be slightly higher than that of the carbodiimide.

In the present invention, the post-treatment is first simple concentration of the reaction solution, and the concentration process of the reaction solution can be concentrated by using a rotary evaporator. The concentrated product is purified, and a certain polarity solvent can be used as the eluent in the purification process, and the chromatographic column can be separated. The selected eluent varies according to the different polarities of the products. Under normal circumstances, the volume ratio of the eluent is petroleum ether:ethyl acetate=6:1 mixed solvent. The chromatographic column used is such as silica gel column or high performance liquid chromatography commonly used in laboratory.

On the other hand, the present invention also provides the application of the compound of the present invention in the synthesis of benzimidazoimidazolone derivatives.

When R ⁴ =H in formula IV, R ¹ = R ² = When, the basic reaction formula of above-mentioned synthetic process is as follows:

In the formula,

R ³ , R ⁵ and R ⁶ are the same or different, and represent substituted or unsubstituted C _1-12 hydrocarbyl, substituted or unsubstituted C _1-12 alkoxy, substituted or unsubstituted C _2-12 alkoxycarbonyl , substituted or unsubstituted C _6-12 aryl group, unsubstituted C _3-7 heterocyclic group or C _3-7 heterocyclic group substituted on the heterocyclic ring; Substituents are selected from hydrogen atom, halogen, pseudohalogen , nitro, trifluoromethyl, carbonyl, ester or amide functional groups.

The compound 2-aminoimidazolone of the present invention has a relatively wide range of uses in the field of organic synthesis, and can be used for synthesizing various heterocyclic compounds, for synthesizing biologically active molecules, for synthesizing other known and unknown compounds, for Drug screening, synthesis and development for the synthesis of biologically active molecules, as well as for the synthesis of known and unknown novel materials, etc.

The invention utilizes carbodiimide, hydrochloride of amino acid ester, zinc trifluoromethanesulfonate and tertiary amine to prepare 2-amino-substituted imidazolone derivatives, the yield is high, and the synthesis method is scientific and reasonable, thereby providing a General method for the synthesis of imidazolone derivatives with various substituents. The method has cheap and easy-to-obtain raw materials, wide application range, high separation yield, simple and easy experimental equipment and operation, and is convenient for further development and application.

Detailed ways

The present invention is further described below in conjunction with the examples, but does not limit the scope of the present invention in any way.

Example 1 - Preparation of compound represented by formula IIIa (R ¹ =R ² =Cy, R ³ =R ⁴ =H):

At room temperature, 1.05 mmol of glycine ethyl ester hydrochloride, 1.05 mmol of triethylamine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of benzene was added to dissolve. Then, 1.0 mmol of N,N'-dicyclohexylcarbodiimide was added, and the reaction was carried out at 80 °C for 8 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 239 mg of imidazolone derivative (IIIa) (purity>98%, yellow solid). rate 91%.

The nuclear magnetic data of this compound are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 1.24 (d, J=6.2 Hz, 6H, CH ₃ ), 1.42, (d, J=7.0 Hz, 6H, CH ₃ ), 3.92 (s, 2H, CH ₂ ), 4.13-4.25 (m, 2H, CH); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 19.73, 22.85, 43.56, 55.76, 60.09, 155.35, 180.22.

Example 2 - Preparation of compound represented by formula IIIb (R ¹ =R ² =4-MeC ₆ H ₄ , R ³ =R ⁴ =H):

At room temperature, 1.05 mmol of glycine ethyl ester hydrochloride, 1.05 mmol of triethylamine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of benzene was added to dissolve. Then, 1.0 mmol of N,N'-di-p-methylphenylcarbodiimide was added, and the reaction was carried out at 80°C for 8 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 262 mg of imidazolone derivative (IIIb) (purity>98%, yellow solid). rate 94%.

The NMR data of this compound are as follows: ¹ H NMR (400MHz, CDCl ₃ ): δ 2.29 (s, 3H, CH ₃ ), 2.38 (brs, 3H, CH ₃ ), 3.90 (brs, 1H, CH ₂ ), 4.22 (brs, 1H, CH ₂ ), 4.38 (brs, 1H, NH), 6.81-6.83 (m, 2H, CH), 7.07-7.09 (m, 2H, CH), 7.24-7.29 (m, 4H, CH) ; ¹³ C NMR (100MHz, CDCl ₃ ): δ20.72, 21.15, 46.90, 119.55, 120.01, 127.11, 129.73, 130.88, 132.42, 138.25, 144.75, 150.82, 170.64.

Example 3 - Preparation of compound represented by formula IIIc (R ¹ =Bn, R ² =2,6- ⁱ PrC ₃ H ₆ , R ³ =R ⁴ =H):

At room temperature, 1.05 mmol of glycine ethyl ester hydrochloride, 1.05 mmol of 4-(N,N-dimethylamino) pyridine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of benzene was added. dissolve. Then, 1.0 mmol of 1-benzyl-3-(2,6-diisopropylphenyl)diimine was added, and the reaction was carried out at 50° C. for 4 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 255 mg of imidazolone derivative (IIIc) (purity>98%, yellow solid). rate 71%.

The NMR data of this compound are as follows: ¹ H NMR (400MHz, CDCl ₃ ): δ 1.08-1.10 (m, 12H, CH ₃ ), 2.82-2.89 (m, 2H, CH ), 3.85 (s, 2H, CH _{2 )} ), 4.25(brs, 1H, NH), 4.91(s, 2H, CH ₂ ), 7.00-7.10(m, 3H, CH), 7.27-7.34(m, 3H, CH), 7.50-7.52(m, 2H , CH); ¹³ C NMR (100MHz, CDCl ₃ ): δ23.39, 23.42, 28.08, 42.61, 46.90, 123.20, 123.51, 127.59, 128.34, 128.63, 136.48, 139.81, 142.02, 147.92, 170.98.

Example 4 - Preparation of compound represented by formula IIId (R ¹ =R ² =Cy, R ³ =Me, R ⁴ =H):

At room temperature, 1.05 mmol of ethyl alanine hydrochloride, 1.05 mmol of triethylamine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of benzene was added to dissolve. Then, 1.0 mmol of N,N'-dicyclohexylcarbodiimide was added, and the reaction was carried out at 100°C for 10 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 225 mg of imidazolone derivative (IIId) (purity>98%, yellow solid). rate 83%.

The nuclear magnetic data of this compound are as follows: ¹ H NMR (400MHz, CDCl ₃ ): δ1.10-1.35 (m, 13H, 5CH ₂ , 1CH ₃ ), 1.54-1.67 (m, 6H, CH ₂ ), 1.77-1.98 ( m, 4H, CH ₂ ), 3.61 (brs, 1H, CH), 3.95 (q, J=7.2 Hz, 1H, CH), 4.02-4.08 (brs, 1H, CH); ¹³ C NMR (100 MHz, CDCl ₃ ):δ13.97,17.53,18.02,24.59,24.77,24.97,25.49,25.63,25.79,29.04,33.79,51.01,51.98,60.17,157.02,174.81.

Example 5 - Preparation of compound represented by formula IIIe (R ¹ =R ² = _i Pr, R ³ =Me, R ⁴ =CH ₂ SH):

At room temperature, 1.05 mmol of cysteine ethyl ester hydrochloride, 1.05 mmol of triethylamine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of tetrahydrofuran was added to dissolve. Then, 1.0 mmol of N,N'-diisopropylcarbodiimide was added, and the reaction was carried out at 80°C for 10 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 132 mg of imidazolone derivative (IIIe) (purity>98%, yellow solid). rate 67%.

The NMR data of this compound are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 1.12 (d, J=6.4 Hz, 3H, CH ₃ ), 1.24 (d, J=6.4 Hz, 3H, CH ₃ ), 1.34 ,(d,J=7.2Hz,6H,CH ₃ ),2.30-(d,J=7.0Hz,2H,CH ₂ ),3.86-3.94(m,2H,CH),4.19(brs,1H,CH) , 5.00-5.01 (m, 1H, NH); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 17.95, 19.74, 22.93, 23.09, 23.30, 41.44, 43.49, 157.26, 174.82.

Example 6 - Preparation of compound represented by formula IIIf (R ¹ =R ² =Cy, R ³ =Bn, R ⁴ =H):

At room temperature, 1.05 mmol of phenylalanine ethyl ester hydrochloride, 1.05 mmol of triethylamine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of tetrahydrofuran was added to dissolve. Then, 1.0 mmol of N,N'-dicyclohexylcarbodiimide was added, and the reaction was carried out at 80°C for 8 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 290 mg of imidazolone derivative (IIIf) (purity>98%, yellow solid). rate 82%.

The NMR data of this compound are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 1.13-1.27 (m, 8H, CH ₂ ), 1.34-1.43 (m, 4H, CH ₂ ), 1.61-1.71 (m, 8H , CH ₂ ), 3.14 (d, J=6.4Hz, 2H, CH ₂ ), 3.36 (brs, 1H, CH), 3.73 (brs, 2H, CH), 4.20 (brs, 1H, NH), 7.10-7.18 (m, 5H, CH); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 24.25, 24.65, 24.87, 25.05, 25.58, 25.84, 29.83, 33.07, 33.26, 33.90, 37.75, 49.96, 51.65, 65.87, 126.18, 127.33, 130.22, 136.05, 154.25, 181.36.

Example 7 - Preparation of compound represented by formula IIIf (R ¹ =R ² =Cy, R ³ =Bn, R ⁴ =H):

At room temperature, 1.05 mmol of ethyl tyrosine hydrochloride, 1.05 mmol of triethylamine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of toluene was added to dissolve. Then, 1.0 mmol of N,N'-dicyclohexylcarbodiimide was added, and the reaction was carried out at 80°C for 8 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 290 mg of imidazolone derivative (IIIf) (purity>98%, yellow solid). rate 82%.

The NMR data of this compound are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 1.13-1.27 (m, 8H, CH ₂ ), 1.34-1.67 (m, 12H, CH ₂ ), 3.14 (d, J=6.4 Hz, 2H, CH ₂ ), 3.36 (brs, 1H, CH), 3.73 (brs, 2H, CH), 4.20 (brs, 1H, NH), 4.20 (brs, 1H, OH), 7.10-7.14 (m, 4H, CH); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 24.15, 24.63, 24.87, 25.14, 25.58, 25.85, 29.83, 33.07, 33.26, 34.01, 37.75, 49.96, 51.67, 65.87, 126.18, 127.36, 131 ,134.05,158.55,181.36.

Example 8 - Preparation of compound represented by formula IIIg (R ¹ =R ² =Cy, R ³ =R ⁴ =-(CH ₂ ) ₃ -):

At room temperature, 1.05 mmol of ethyl proline ester hydrochloride, 1.05 mmol of triethylamine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, and 5 mL of benzene was added to dissolve. Then, 1.0 mmol of N,N'-dicyclohexylcarbodiimide was added, and the reaction was carried out at 80°C for 8 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 215 mg of imidazolone derivative (IIIg) (purity>98%, colorless solid), which was isolated Yield 71%.

The NMR data of this compound are as follows: ¹ H NMR (400MHz, CDCl ₃ ): δ1.24-1.27 (m, 1H, CH ₂ ), 1.84-1.98 (m, 2H, CH ₂ ), 2.29-2.30 (m, 1H , CH ₂ ), 2.94 (brs, 2H, CH ₂ ), 3.90 (t, J=8.0 Hz, 1H, CH), 6.93-7.01 (m, 3H, CH), 7.22-7.26 (m, 2H, CH) , 7.32-7.34 (m, 1H, CH), 7.46 (brs, 4H, CH); ¹³ CNMR (100MHz, CDCl ₃ ): δ27.23, 28.63, 50.20, 64.76, 122.17, 122.34, 127.14, 128.00, 128.70, 128.84, 132.87, 147.81, 152.39, 172.77.

Example 9 - Preparation of compound represented by formula IVh (R ¹ =R ² =Ph, R ³ =R ⁴ =-(CH ₂ ) ₃ -):

At room temperature, 1.05 mmol of proline ethyl ester hydrochloride, 1.05 mmol of 4-(N,N'-dimethylamino)pyridine and 0.05 mmol of zinc trifluoromethanesulfonate were added to a 25 mL reaction tube, Add 5mL of benzene to dissolve. Then, 1.0 mmol of N,N'-bis(p-chlorophenyl)carbodiimide was added, and the reaction was carried out at 50°C for 4 hours. The reaction system was a yellow suspension. The reaction solution was concentrated, decolorized and separated on a silica gel column, and the mixed solvent of petroleum ether:ethyl acetate=6:1 was used as the eluent to obtain 215 mg of imidazolone derivative (IIIh) (purity>98%, colorless solid), which was isolated Yield 71%.

The NMR data of this compound are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 1.24-1.27 (m, 1H, CH ₂ ), 1.84-1.98 (m, 2H, CH ₂ ), 2.29-2.30 (m, 1H , CH ₂ ), 2.94 (brs, 2H, CH ₂ ), 3.90 (t, J=8.0Hz, 1H, CH), 6.93-7.01 (m, 3H, CH), 7.32-7.34 (m, 1H, CH) , 7.46 (brs, 4H, CH); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 27.23, 28.63, 50.20, 64.76, 122.17, 122.34, 127.14, 128.00, 128.70, 128.84, 132.87, 147.77.

Synthetic Application Example - Preparation of Compounds of Formula V

At room temperature, 1.0 mmol of imidazolone derivative (IIIb) was added to a 25 mL reaction tube, 5 mL of acetonitrile was added to dissolve, 1.0 mmol of PhI(OAc) ₂ was added, and the reaction was carried out at 80° C. for 2 h. After the reaction was completed, the system was lowered to room temperature, and the silica gel column was decolorized and separated, and the mixed solvent of petroleum ether:ethyl acetate=2:1 was used as the eluent to obtain 233 mg of benzimidazoimidazolone derivative (V) (purity>98 %, yellow solid) in 84% isolated yield.

The NMR data of this compound are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 2.40 (s, 3H, CH ₃ ), 2.47 (s, 3H, CH ₃ ), 4.68 (s, 2H, CH ₂ ), 7.03 -7.05(m, 2H, CH), 7.33(d, J=8.2Hz, 2H, CH), 7.55(d, J=8.2Hz, 1H, CH), 7.70(d, J=8.4Hz, 2H, CH) ); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 21.17, 21.64, 47.49, 108.74, 119.06, 123.54, 123.76, 129.85, 130.01, 131.62, 132.43, 137.99, 142.12, 153.61, 170.00.

Claims (9)

1. A method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of glycine ethyl ester hydrochloride, 1.05mmol of triethylamine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of benzene for dissolving, then adding 1.0mmol of N, N' -dicyclohexylcarbodiimide, reacting for 8 hours at 80 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, decoloring and separating by a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 239mg of imidazolone derivative shown in the following formula with the purity of more than 98 percent, separating yellow solid with the separation yield of 91 percent,

2. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of glycine ethyl ester hydrochloride, 1.05mmol of triethylamine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of benzene for dissolving, then adding 1.0mmol of N, N' -di-p-methylphenyl carbodiimide, reacting for 8 hours at 80 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, decoloring and separating by a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 262mg of imidazolone derivative (IIIb), the purity is more than 98 percent, obtaining yellow solid, the separation yield is 94 percent,

3. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of glycine ethyl ester hydrochloride, 1.05mmol of 4- (N, N-dimethylamino) pyridine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of benzene for dissolving, then adding 1.0mmol of 1-benzyl-3- (2, 6-diisopropylphenyl) diimine, reacting for 4 hours at 50 ℃, concentrating the reaction system to obtain a yellow suspension, decolorizing and separating the reaction solution by a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate 6:1 as an eluent to obtain 255mg of imidazolone derivative (IIIc) with the purity of 98 percent and a yellow solid with the separation yield of 71 percent,

4. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of alanine ethyl ester hydrochloride, 1.05mmol of triethylamine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of benzene for dissolving, then adding 1.0mmol of N, N' -dicyclohexylcarbodiimide, reacting for 10 hours at 100 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, decoloring and separating by a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 225mg of imidazolone derivative (IIId), the purity is more than 98 percent, obtaining yellow solid, the separation yield is 83 percent,

5. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of cysteine ethyl ester hydrochloride, 1.05mmol of triethylamine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of tetrahydrofuran for dissolving, then adding 1.0mmol of N, N' -diisopropyl carbodiimide, reacting for 10 hours at 80 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, decoloring and separating by a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 132mg of imidazolone derivative (IIIe), the purity is more than 98%, a yellow solid, the separation yield is 67%,

6. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of phenylalanine ethyl ester hydrochloride, 1.05mmol of triethylamine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of tetrahydrofuran for dissolving, then adding 1.0mmol of N, N' -dicyclohexylcarbodiimide, reacting for 8 hours at 80 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, decoloring and separating by using a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 290mg of imidazolone derivative (IIIf), the purity is more than 98%, obtaining yellow solid, the separation yield is 82%,

7. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of tyrosine ethyl ester hydrochloride, 1.05mmol of triethylamine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of toluene for dissolving, then adding 1.0mmol of N, N' -dicyclohexylcarbodiimide, reacting for 8 hours at 80 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, decoloring and separating by a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 290mg of imidazolone derivative (IIIf), the purity is more than 98 percent, separating the yield to be 82 percent,

8. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of proline ethyl ester hydrochloride, 1.05mmol of triethylamine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of benzene for dissolving, then adding 1.0mmol of N, N' -dicyclohexylcarbodiimide, reacting for 8 hours at 80 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, decoloring and separating by using a silica gel column, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 215mg of imidazolone derivative (IIIg), the purity is more than 98%, and a colorless solid, the separation yield is 71%,

9. a method for synthesizing an imidazolone derivative comprises the following steps:

adding 1.05mmol of proline ethyl ester hydrochloride, 1.05mmol of 4- (N, N '-dimethylamino) pyridine and 0.05mmol of zinc trifluoromethanesulfonate into a 25mL reaction tube at room temperature, adding 5mL of benzene for dissolving, then adding 1.0mmol of N, N' -di (p-chlorophenyl) carbodiimide, reacting for 4 hours at 50 ℃, wherein the reaction system is yellow suspension, concentrating the reaction solution, carrying out silica gel column decoloration and separation, using a mixed solvent of petroleum ether and ethyl acetate which is 6:1 as an eluent, obtaining 215mg of imidazolone derivative (IIIh), the purity is more than 98%, and the separation yield is 71%,