Precursor structure design and preparation method of novel tracer 11C-UCB-J

Abstract

The invention discloses a precursor structure design of a novel tracer 11C-UCB-J and a preparation method thereof. The precursor structure design comprises a compound shown as a formula (I) and pharmaceutically acceptable salts, esters, amides or other derivative forms of the compound; the center of the compound is a pyrrolidine ring, and a ketone group is connected to the site 2 of the pyrrolidine ring; a benzene ring is connected to the position 3 of a pyrrolidine ring, and three fluorine atoms are arranged on the benzene ring, so that a trifluoromethyl mode is formed; a pyridine ring is connected to the fourth position of a pyrrolidine ring; a tin substituent is connected to a pyridine ring, and the tin substituent has three alkyl groups R1, R2 and R3. According to the invention, a novel 11C-UCB-J precursor PSP is designed and synthesized, and an efficient Stille coupling reaction is realized under the action of a palladium catalyst by using mild alkali and a stable organic tin reagent through an optimized two-step synthesis route; the synthesis process is simplified, the yield and the purity are improved, the chemical stability of the precursor is remarkably enhanced, and the precursor is convenient to store and transport.

Description

Technical Field

[0001] The present invention relates to the technical field of tracers, and in particular to a novel tracer. 11 Precursor structure design and preparation method of C-UCB-J. Background Art

[0002] Synaptic Vesicle Glycoprotein 2A (SV2A) is a transmembrane protein that plays a key role in brain nerve cells. It is located on synaptic vesicles that are responsible for transmitting information. These synaptic vesicles store and release neurotransmitters in a timely manner to transmit nerve signals from one cell to the next. The number of SV2A can be used as an indicator to evaluate the density of nerve endings and is an important parameter for measuring the structural and functional characteristics of synapses. Its normal function is essential for maintaining effective synaptic transmission. The absence or abnormality of SV2A may lead to synaptic transmission disorders, which are closely related to the occurrence of various neuropsychiatric diseases.

[0003] The absence or abnormality of SV2A is associated with a variety of neuropsychiatric diseases, including epilepsy, Alzheimer's disease and schizophrenia; when the function of SV2A is impaired, it may cause excessive excitation of neurons, thereby triggering epileptic seizures; abnormalities in SV2A interfere with the normal physiological function of synaptic vesicles, causing changes in postsynaptic membrane potential, and is one of the causes of symptoms of neurodegenerative diseases such as Alzheimer's disease; changes in SV2A expression levels disrupt the normal release of neurotransmitters and effective transmission between synapses, and have a potential impact on the symptoms of schizophrenia; therefore, studying the function and status of SV2A is of great significance for understanding the pathogenesis of these diseases.

[0004] PET is an imaging technique for nuclear medicine clinical examinations that uses positrons and gamma rays produced by the decay of radioactive nuclides to study molecular metabolism and functional activities in the body. During a PET scan, patients with neuropsychiatric diseases are injected with tracers, which emit positrons in the body. When the positrons meet electrons, they are annihilated and release two beams of gamma rays with an energy of 511keV. After the PET scanner captures these two beams of gamma rays, a computer algorithm is used to generate functional images of tissues or organs.

[0005] 11 C-UCB-J is a PET radiotracer with high affinity and selectivity for SV2A. It can be detected by PET scanners in a short time, thus achieving dynamic tracking and imaging of SV2A, allowing researchers and clinicians to evaluate changes in synaptic function involved in neuropsychiatric diseases. 11 The short radioactive half-life caused by C 11C-UCB-J cannot be transported for long periods of time, cannot be used in telemedicine or decentralized medical facilities, and needs to be made and used immediately in clinical practice, which limits the 11 Application of C-UCB-J in the field of neuropsychiatric diseases.

[0006] Therefore, it is necessary to 11 The precursor structure design of C-UCB-J and its preparation method are improved to solve the above problems. Summary of the invention

[0007] The present invention overcomes the shortcomings of the prior art and provides a new type of tracer 11 The precursor structure design and preparation method of C-UCB-J are intended to solve the problems in the prior art. 11 The C-UCB-J synthesis route has problems such as insufficient stability, low reaction efficiency and complex purification process.

[0008] 2. To achieve the above purpose, the technical solution adopted by the present invention is: a new type of tracer 11 The precursor structure design of C-UCB-J and the preparation method thereof include: a compound of formula (I) in the form of a pharmaceutically acceptable salt, ester, amide or other derivative thereof;

[0009]

[0010] The center of the compound is a pyrrolidine ring with a keto group attached to the 2-position of the pyrrolidine ring;

[0011] At the 3-position of the pyrrolidine ring, a benzene ring is attached with three fluorine atoms, forming a trifluoromethyl pattern;

[0012] At the 4-position of the pyrrolidine ring, a pyridine ring is attached;

[0013] Attached to the pyridine ring is a tin substituent carrying three alkyl groups R1, R2 and R3.

[0014] In a preferred embodiment of the present invention, R1, R2, and R3 are C1-C18 alkyl groups; C1-C18 alkyl groups are straight-chain or branched alkane groups consisting of 1 to 18 carbon atoms.

[0015] The present invention provides a novel tracer 11 The method for preparing a precursor of C-UCB-J comprises the following steps:

[0016] S1, using R-4-(3,4,5-trifluorophenyl)pyrrole-2-one as a raw material, reacting with 3-bromo-4-chloromethylpyridine hydrochloride in the presence of a base and a solvent to generate R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one;

[0017] S2, R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one is subjected to Stille coupling reaction with an organotin reagent under the catalysis of a palladium reagent to generate the target product 11 C-UCB-J precursor.

[0018] In a preferred embodiment of the present invention, in step S1, the base is an inorganic base, including sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide and sodium hydride; the solvent is one of methanol, ethanol, N,N-dimethylformamide, acetone and acetonitrile.

[0019] In a preferred embodiment of the present invention, in step S1, the reaction temperature is 20-80°C; and the reaction time is 10-24h.

[0020] In a preferred embodiment of the present invention, in step S1, the molar ratio of R-4-(3,4,5-trifluorophenyl)pyrrole-2-one, 3-bromo-4-chloromethylpyridine hydrochloride and sodium carbonate is 1:1.2:3.

[0021] In a preferred embodiment of the present invention, in step S2, the palladium reagent is one of tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, 1,1'-bis(diphenylphosphinodiphenylphosphinocene)palladium dichloride and bis(dibenzylideneacetone)palladium.

[0022] In a preferred embodiment of the present invention, in step S2, the tin reagent is one of trialkyltin halide and hexaalkylditin; and the solvent is one of DMF, acetone, acetonitrile, tetrahydrofuran, 1,4-dioxane and toluene.

[0023] In a preferred embodiment of the present invention, in step S2, the molar ratio of R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one, hexamethylditin and tetrakis(triphenylphosphine)palladium is 1:3:0.2.

[0024] In a preferred embodiment of the present invention, in step S2, the reaction temperature is 50-100° C. and the reaction time is 4-18 h.

[0025] The present invention solves the defects existing in the background technology and has the following beneficial effects:

[0026] (1) The present invention designs and synthesizes a novel11 The C-UCB-J precursor PSP achieves an efficient Stille coupling reaction through an optimized two-step synthesis route, using mild bases and stable organotin reagents under the action of palladium catalysts; it not only simplifies the synthesis process, improves the yield and purity, but also significantly enhances the chemical stability of the precursor, making it easier to store and transport. In addition, the rapid and mild methylation conditions greatly shorten the reaction time, reduce radioactive decay losses, and increase the effective radiation dose, thereby better meeting the needs of ready-to-use in clinical applications.

[0027] (2) The present invention optimizes the 11 The chemical stability of the C-UCB-J precursor is that the precursor structure is based on the pyrrolidine ring, and a keto group, a trifluoromethylbenzene ring, a pyridine ring, and a tin substituent with three alkyl groups are introduced at different positions; this structural design not only improves the chemical stability of the precursor, but also ensures that key functional groups such as the keto group and the trifluorobenzene ring are not damaged during the entire synthesis process, realizing the feasibility of long-term storage and long-distance transportation. Compared with the problem of insufficient precursor stability in the prior art, it further expands 11 The application scope of C-UCB-J in the field of neuropsychiatric diseases.

[0028] (3) The present invention adopts Stille coupling reaction to couple R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one with an organic tin reagent under the action of a palladium catalyst to generate the target product 11 The C-UCB-J precursor simplifies the synthesis process and improves the reaction efficiency. Compared with the Suzuki coupling reaction used in the prior art, the Stille reaction conditions are milder, the reaction time is shorter, and the complicated purification process is avoided, thereby reducing the production cost and improving the production efficiency.

[0029] (4) The present invention ensures the novel 11 The C-UCB-J precursor has higher chemical stability. In step S1, mild sodium carbonate is used as a base to avoid violent side reactions and protect sensitive functional groups such as ketone groups and trifluorobenzene rings. In addition, the selection of a stable organic tin reagent for the Stille coupling reaction in step S2 further enhances the stability of the precursor, allowing the precursor to maintain its structural integrity for a longer period of time, making it easier to store and transport over long distances. Compared with the prior art, this further achieves the effect of extending the shelf life and simplifying logistics management. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art are briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative work.

[0031] Figure 1 is a precursor synthesis route diagram of a preferred embodiment of the present invention;

[0032] Figure 2 It is a specific experimental synthesis route diagram of a preferred embodiment of the present invention. DETAILED DESCRIPTION

[0033] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein. Therefore, the protection scope of the present invention is not limited to the specific embodiments disclosed below.

[0035] Application Overview:

[0036] 11 C-UCB-J was synthesized by reacting the precursor with radiolabeled methyl iodide. 11 CH3I completes the chemical reaction in one step; 11 The half-life of C is only 20.4 minutes, and its short existence time leads to 11 C-UCB-J cannot be stored for a long time or transported over long distances, so it needs to be used immediately in clinical applications. To meet this requirement, 11 The precursor of C-UCB-J must be sufficiently stable to ensure that it can be easily stored and transported. In addition, from a practical point of view, the precursor 11 The reaction conditions between CH3I should be simple and easy to carry out, and the reaction speed should be fast enough to ensure that the effective radiation dose can be maintained while generating 11 C-UCB-J.

[0037] However, currently 11 The main synthetic route of C-UCB-J is to use boric acid, alkyl borate or trifluoroborate as precursors and react with it through Suzuki coupling reaction.11 There are several limitations to the CH3I conjugation approach; the stability of these precursors themselves is low, which complicates handling and storage, and they are 11 The reaction efficiency of CH3I is low, and the conversion rate is low, which leads to a longer reaction time. In addition, the purification process of these precursors is also cumbersome, which further increases the difficulty of synthesis. 11 The widespread use of C-UCB-J in the diagnosis of neuropsychiatric disorders poses a barrier.

[0038] To this end, this application proposes a new type of tracer 11 The precursor structure design and preparation method of C-UCB-J solve the existing 11 The C-UCB-J synthesis route has problems such as insufficient stability, low reaction efficiency and complex purification process.

[0039] Exemplary Precursor Structure Design:

[0040] The present invention provides a novel tracer 11 The precursor structure design of C-UCB-J includes: a compound of formula (I) in the form of a pharmaceutically acceptable salt, ester, amide or other derivative thereof;

[0041]

[0042] The center of the compound is a pyrrolidine ring with a keto group attached to the 2-position of the pyrrolidine ring;

[0043] At the 3-position of the pyrrolidine ring, a benzene ring is attached with three fluorine atoms, forming a trifluoromethyl pattern;

[0044] At the 4-position of the pyrrolidine ring, a pyridine ring is attached;

[0045] Attached to the pyridine ring is a tin substituent with three alkyl groups R1, R2 and R3;

[0046] Among them, R1, R2, and R3 are C1-C18 alkyl groups; C1-C18 alkyl groups are straight-chain or branched alkane groups composed of 1 to 18 carbon atoms. The presence of the alkyl group can enhance the lipid solubility of the compound, making it easier for it to pass through the biological membrane and enter the cell.

[0047] Exemplary Precursor Preparation Methods:

[0048] like Figure 1 As shown, a new type of tracer 11 The precursor of C-UCB-J and the preparation method thereof include:

[0049] S1, using R-4-(3,4,5-trifluorophenyl)pyrrole-2-one as a raw material, reacting with 3-bromo-4-chloromethylpyridine hydrochloride in the presence of a base and a solvent to generate R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one;

[0050] S2, subjecting R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one to a Stille coupling reaction with an organotin reagent under the catalysis of a palladium reagent to generate a target product 11C-UCB-J precursor;

[0051] In step S1, the base is one of the inorganic bases, including: sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide and sodium hydride; preferably, the base is sodium carbonate; the reaction of sodium carbonate is relatively mild and will not cause a violent exothermic reaction or trigger the decomposition of other sensitive functional groups, which is very important for protecting the keto group and trifluorobenzene ring in the starting material R-4-(3,4,5-trifluorophenyl)pyrrole-2-one, and avoiding the formation of possible by-products.

[0052] The base can neutralize the hydrochloric acid in 3-bromo-4-chloromethylpyridine hydrochloride to generate a more active chloromethyl compound, thereby increasing its activity as an electrophilic reagent and facilitating the subsequent nucleophilic substitution reaction with R-4-(3,4,5-trifluorophenyl)pyrrole-2-one;

[0053] The nitrogen atom of the starting material R-4-(3,4,5-trifluorophenyl)pyrrole-2-one combines with the chloromethyl part of 3-bromo-4-chloromethylpyridine hydrochloride through a nucleophilic substitution reaction to form a new CN bond, and retains the original keto group and trifluorobenzene ring. The N atom has a higher electronegativity and smaller steric hindrance, and the formed CN bond is relatively stable and not easy to break.

[0054] In step S1, the solvent is one of methanol, ethanol, N,N-dimethylformamide, acetone and acetonitrile; preferably, the solvent is N,N-dimethylformamide; N,N-dimethylformamide provides good solubility and, as an inert solvent, does not interfere with the reaction process, reducing the possibility of unnecessary side reactions.

[0055] In step S1, the reaction temperature is 20-80°C, preferably 60°C, which can ensure the reaction speed while avoiding side reactions or functional group decomposition caused by excessively high temperature; in addition, N,N-dimethylformamide maintains good stability and solubility within this temperature range; the reaction time is 10-24h, preferably 12h.

[0056] Step S1 introduces a connection point, i.e., a bromopyridine moiety, on the starting material that can be used for a subsequent coupling reaction, and protects sensitive functional groups, such as a keto group and a trifluorobenzene ring, to prevent them from undergoing unnecessary side reactions or decomposition during the process.

[0057] In step S2, the palladium reagent is one of tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride and bis(dibenzylideneacetone)palladium; preferably, the palladium reagent is tetrakis(triphenylphosphine)palladium, and the zero-valent palladium complex has high activity, good stability and wide applicability, and can quickly start and efficiently catalyze the coupling reaction without the need for an additional reducing agent.

[0058] In step S2, the tin reagent is one of a trialkyl tin halide and a hexaalkyl ditin; preferably, the tin reagent is hexamethyl ditin, which provides a stable tin source and its structural characteristics help to improve the selectivity and yield of the reaction; the palladium catalyst promotes the Stille coupling reaction, so that the bromopyridine part and the organic tin reagent undergo a cross-coupling reaction to form a new CC bond, while releasing halogen ions;

[0059] In step S2, the solvent is one of DMF, acetone, acetonitrile, tetrahydrofuran, 1,4-dioxane and toluene; preferably, the solvent is acetonitrile; acetonitrile, as a polar solvent, can dissolve all reactants well, provide a homogeneous reaction environment, and help improve the reaction efficiency and yield.

[0060] In step S2, the bromine atom in R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one is replaced by the carbon atom in the organotin reagent to form a new CC bond, and the original ketone group and trifluorophenyl ring are retained. Through step S2, not only the successful conversion from the intermediate to the target product is achieved, but also the radiolabeling site is introduced. 11 C is ready.

[0061] In step S2, the reaction temperature is 50-100°C, preferably 80°C; the reaction time is 4-18h, preferably 8h. Specific embodiment:

[0063] like Figure 2 As shown, the preparation steps of R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one include:

[0064] Prepare a clean, dry 150mL three-necked flask equipped with a stirring device, a thermometer and a reflux condenser;

[0065] 2.0 g of R-4-(3,4,5-trifluorophenyl)pyrrole-2-one, 2.71 g of 3-bromo-4-chloromethylpyridine hydrochloride and 2.96 g of sodium carbonate were added to a three-necked flask in sequence; the molar ratio of R-4-(3,4,5-trifluorophenyl)pyrrole-2-one, 3-bromo-4-chloromethylpyridine hydrochloride and sodium carbonate was 1:1.2:3;

[0066] Slowly add 50 mL of N,N-dimethylformamide to ensure that all solids are completely dissolved;

[0067] The reaction mixture was heated to 60° C. and stirred for 12 hours, and the reaction progress was monitored by TLC until it was confirmed that the starting material R-4-(3,4,5-trifluorophenyl)pyrrole-2-one had been completely reacted;

[0068] After the reaction was completed, the heating was stopped, and the reaction solution was allowed to cool naturally to room temperature. 100 ml of water was added to the reaction bottle. A large amount of white precipitate was generated. Stirring was continued for 1 hour to ensure that the precipitate was completely formed.

[0069] The white precipitate was collected by suction filtration, and the filter cake was rinsed with 50 ml of water three times to remove the residual impurities and solvents. The filter cake was placed in a 60°C forced air oven and dried for 6 hours until constant weight was reached;

[0070] The dried solid was dissolved in dichloromethane and separated and purified by column chromatography. The eluent was a mixture of DCM, MeOH and NH4OH, and the ratio of DCM:MeOH:NH4OH was 97.5:2:0.5. The eluate containing the target product was collected and concentrated under reduced pressure to obtain a pure intermediate.

[0071] 1.51 g of white solid, namely R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one, was obtained with a yield of 42.3%.

[0072] 11 The preparation steps of the C-UCB-J precursor include:

[0073] Prepare a clean, dry 150mL three-necked flask equipped with a stirring device, a thermometer and a nitrogen protection system;

[0074] Under nitrogen protection, add 1.0 g of R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one and 20 ml of acetonitrile into a three-necked flask and stir until completely dissolved;

[0075] Add 2.55 g of hexamethyltin and 600 mg of tetrakis(triphenylphosphine)palladium in sequence, making sure to stir thoroughly after each addition;

[0076] The molar ratio of R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one, hexamethylditin and tetrakis(triphenylphosphine)palladium is 1:3:0.2;

[0077] The reaction mixture was heated to 80°C and stirred continuously at this temperature for 8 hours, maintaining a nitrogen atmosphere to prevent oxidation;

[0078] After the reaction was completed, the heating was stopped, the mixture was naturally cooled to room temperature, and 5 g of silica gel was added to facilitate subsequent column chromatography separation. The column chromatography separation and purification reduced the generation of impurities and improved the product quality.

[0079] The solvent was removed by distillation under reduced pressure to obtain a residual solid, which was separated and purified by column chromatography, with the eluent being a mixture of DCM, MeOH, and NH4OH, with the ratio of DCM:MeOH:NH4OH being 96.5:3:0.5; the eluate containing the target product was collected, and concentrated under reduced pressure to obtain a pure target compound;

[0080] 0.98 g of white solid was obtained. 11 The precursor of C-UCB-J was obtained with a yield of 80.6%.

[0081] The present invention 11 The C-UCB-J precursor has higher chemical stability and can maintain its structural integrity for a long time, making it easy to store and transport over long distances. By selecting a mild base, violent exothermic reactions or decomposition of other sensitive functional groups are avoided, ensuring that key functional groups are not damaged throughout the synthesis process, thereby improving the stability of the final precursor. The solvent not only provides good solubility but is also inert and will not produce unnecessary side reactions with the reactants, further ensuring the stability of the precursor. Separation and purification are carried out by column chromatography, and the selection of eluent is optimized to ensure the effective separation and purification of the target product.

[0082] 11 C-UCB-J was prepared by reacting the precursor with 11 The methylation reaction of CH3I can be completed in just 5 minutes at 60°C using a commercially available palladium catalyst, with a conversion rate of up to 88% to 91%, significantly shortening the reaction time and improving production efficiency.

[0083] The above is based on the ideal embodiment of the present invention. Through the above description, relevant personnel can make various changes and modifications without departing from the technical concept of the present invention. The technical scope of the present invention is not limited to the content in the specification, and the technical scope must be determined according to the scope of the claims.

Claims

1. A new type of tracer 11 The precursor structure design of C-UCB-J is characterized by: include: The compound of formula (I) in the form of pharmaceutically acceptable salts, esters, amides or other derivatives; The center of the compound is a pyrrolidine ring with a keto group attached to the 2-position of the pyrrolidine ring; At the 3-position of the pyrrolidine ring, a benzene ring is attached with three fluorine atoms, forming a trifluoromethyl pattern; At the 4-position of the pyrrolidine ring, a pyridine ring is attached; Attached to the pyridine ring is a tin substituent carrying three alkyl groups R1, R2 and R3.

2. A novel tracer according to claim 1 11 The precursor structure design of C-UCB-J is characterized by: R1, R2, and R3 are C1-C18 alkyl groups; C1-C18 alkyl groups are straight-chain or branched alkane groups consisting of 1 to 18 carbon atoms.

3. A new type of tracer 11 A method for preparing a precursor of C-UCB-J, a novel tracer according to any one of claims 1 to 2 11 The precursor structure design of C-UCB-J is characterized by: Includes steps: S1, using R-4-(3,4,5-trifluorophenyl)pyrrole-2-one as a raw material, reacting with 3-bromo-4-chloromethylpyridine hydrochloride in the presence of a base and a solvent to generate R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one; S2, R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one is subjected to Stille coupling reaction with an organotin reagent under the catalysis of a palladium reagent to generate the target product 11 C-UCB-J precursor.

4. A novel tracer according to claim 3 11 The method for preparing a precursor of C-UCB-J is characterized by: In step S1, the base is one of inorganic bases, including sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide and sodium hydride; the solvent is one of methanol, ethanol, N,N-dimethylformamide, acetone and acetonitrile.

5. A novel tracer according to claim 3 11 The method for preparing a precursor of C-UCB-J is characterized by: In step S1, the reaction temperature is 20-80°C; and the reaction time is 10-24h.

6. A novel tracer according to claim 3 11 The method for preparing a precursor of C-UCB-J is characterized by: In step S1, the molar ratio of R-4-(3,4,5-trifluorophenyl)pyrrole-2-one, 3-bromo-4-chloromethylpyridine hydrochloride and sodium carbonate is 1:1.2:

3.

7. A novel tracer according to claim 3 11 The method for preparing a precursor of C-UCB-J is characterized by: In step S2, the palladium reagent is one of tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, 1,1'-bis(diphenylphosphinodiphenylphosphinocenepalladium dichloride and bis(dibenzylideneacetone)palladium.

8. A novel tracer according to claim 3 11 The method for preparing a precursor of C-UCB-J is characterized by: In step S2, the tin reagent is one of trialkyltin halide and hexaalkylditin; and the solvent is one of DMF, acetone, acetonitrile, tetrahydrofuran, 1,4-dioxane and toluene.

9. A novel tracer according to claim 3 11 The method for preparing a precursor of C-UCB-J is characterized by: In step S2, the molar ratio of R-1-[(3-bromopyridin-4-yl)methyl]-4-(3,4,5-trifluorophenyl)pyrrole-2-one, hexamethylditin and tetrakis(triphenylphosphine)palladium is 1:3:0.

2.

10. A novel tracer according to claim 1 11 The method for preparing a precursor of C-UCB-J is characterized by: In step S2, the reaction temperature is 50-100° C. and the reaction time is 4-18 h.

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