Aminopyrine-13c2 compound and its synthesis method and use
Patent Information
- Application Number
- CN202611076100.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-07-20
- Publication Date
- 2026-09-15
Smart Images
Figure CN122749409A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of isotope-labeled compound synthesis technology, specifically to an aminopyrine- 13 C2 compounds, their synthesis methods, and applications. Background Technology
[0002] In existing technologies, the isotope-labeled synthesis of aminopyrine typically faces challenges such as harsh reaction conditions, low yields, and the use of expensive or difficult-to-obtain carbon-13 labeled raw materials. Some methods rely on complex multi-step reactions, resulting in poor atom economy and hindering efficient resource utilization. Furthermore, some synthetic routes employ catalyst systems with insufficient activity or poor stability, which can easily trigger side reactions, affecting product purity and yield.
[0003] Another prominent issue is that existing methods for preparing isotope-labeled aminopyrine have significant limitations when scaled up for production. Processes feasible at the laboratory scale often fail to transition smoothly to industrial production, exhibiting increased difficulty in reaction control, reduced safety, more complex post-processing, and significantly higher costs. This limits its widespread application in fields requiring large quantities of stable isotope-labeled compounds, such as pharmaceutical metabolism research and isotope tracing.
[0004] Meanwhile, despite advancements in carbon-13 labeling reagents in recent years, many synthetic routes still fail to fully utilize the currently available, inexpensive carbon-13 precursors (such as...). 13 CO2 or 13 CH3OH-derived formic acid 13 C). Existing methods are not well-suited for these types of highly abundant and stable labeled raw materials, resulting in low raw material utilization and increased overall synthesis costs.
[0005] Therefore, developing a synthetic route that combines readily available and abundant carbon-13 labeled raw materials with high atomic efficiency, mild reaction conditions, simple operation, and good scalability has become crucial for achieving aminopyrine- 13 Key challenges in the efficient preparation of C2. In particular, it is necessary to address the shortcomings of traditional methods, such as unstable yields, poor process reproducibility, and unsuitability for large-scale production, in order to meet the demand for high-quality isotope-labeled compounds in practical applications. Summary of the Invention
[0006] To address the above problems, this invention provides an aminopyrine- 13 The synthesis method of C2 compounds involves using formic acid- 13An innovative method for direct two-site isotopic labeling of 4-aminoantipyrine using C-13 as the labeling source and under the synergistic effect of platinum catalyst and triphenylsilane solves the technical problems of harsh reaction conditions, low yield, high raw material cost, poor atomic efficiency and difficulty in scale-up in the synthesis of aminopyrine isotopic labeling in the prior art.
[0007] This invention includes the following technical solutions: An aminopyrine- 13 A method for synthesizing a C2 compound, wherein two carbon atoms in the compound are labeled with carbon-13 isotopes, and the carbon-13 atoms are derived from formic acid- 13 C. Utilizing formic acid- 13 C, as a cheap and readily available source of carbon-13, allows for the efficient introduction of two carbon-13 atoms into the 4-aminoantipyrine molecule through a catalytic reduction process under mild conditions, achieving the aminopyrine- 13 High-selectivity and high-atomic-efficiency synthesis of C2.
[0008] Alternatively, in the above synthesis method, a catalytic system consisting of a platinum catalyst and a bidentate phosphine ligand is used, with triphenylsilane as the reducing agent, to react formic acid- 13 The carbon-13 atom in C is introduced into the 4-aminoantipyrine molecule to achieve aminopyrine- 13 Synthesis of C2.
[0009] Alternatively, the above synthesis method may include the following steps: under an inert gas atmosphere, 4-aminoantipyrine and formic acid- 13 C is mixed in a solvent; a catalytic system is formed by adding a platinum catalyst and ligands; simultaneously, triphenylsilane is added as a reducing agent to make formic acid- 13 The carbon-13 atom in C is introduced into the 4-aminoantipyrine molecule via a catalytic reduction reaction, generating aminopyrine- 13 C2. The entire reaction is carried out under the protection of an inert gas to ensure the stability and reproducibility of the reaction system.
[0010] Alternatively, in the above synthesis method, the ligand is a bidentate phosphine ligand, preferably 1,3-bis(diphenylphosphine)propane.
[0011] Alternatively, in the above synthesis method, the solvent is a dry ether solvent, preferably dibutyl ether.
[0012] Alternatively, in the above synthesis method, the reaction temperature is 50℃~80℃, preferably 60℃.
[0013] Alternatively, in the above synthesis method, the reaction time is 12 to 24 hours.
[0014] Alternatively, in the above synthesis method, formic acid- 13 C is added to the reaction system in batches.
[0015] As an optional approach, the specific synthetic route in the above synthetic method is as follows: ; Alternatively, the above synthesis method includes the following steps: First, under an argon atmosphere, 1,3-bis(diphenylphosphine)propane is dissolved in dry dibutyl ether, followed by the addition of tetra(triphenylphosphine)platinum catalyst, and stirring to form a slightly yellow solution; after the system is thoroughly mixed, stirring is continued for 10 minutes, and then triphenylsilane is added; immediately afterwards, 4-aminoantipyrine and formic acid are added to the system. 13 C. During the addition of reactants, significant bubble generation was observed, indicating the start of the reaction. The reaction mixture was continuously stirred at a constant temperature of 60°C for 18 hours, during which the reduction and conversion of the carbon-13 labeling was completed. After LCMS confirmed the completeness of the reaction, ethyl acetate was added to dilute the reaction solution, followed by the slow dropwise addition of NaOH aqueous solution and vigorous stirring at room temperature for 3 hours to completely destroy residual reagents and promote product separation. Subsequently, the reaction mixture was extracted three times with ethyl acetate, all organic phases were combined, and dried with anhydrous magnesium sulfate to remove trace amounts of water. The dried organic phase was filtered to remove the desiccant, and then concentrated to remove the solvent, yielding the crude product. Finally, the crude product was recrystallized and purified using n-hexane as a solvent to obtain the pure target product, aminopyrine- 13 C2.
[0016] Alternatively, in the above synthesis method, 1,3-bis(diphenylphosphine)propane acts as a ligand to co-constitute a catalytic system with tetra(triphenylphosphine)platinum, where platinum is the central metal catalyst and the ligand enhances its stability and catalytic activity; triphenylsilane acts as a reducing agent to participate in the hydrogen transfer process, assisting in the realization of formic acid- 13 Efficient transfer of carbon-13 atoms from C to the substrate; formic acid-13C not only provides a carbon-13 labeling source, but also participates in the decarboxylation and reduction steps in the reaction; 4-aminoantipyrine, as the starting substrate, accepts the labeling of two carbon-13 atoms; the entire reaction is carried out homogeneously in dry dibutyl ether to ensure good dissolution and full contact of each component; in the post-processing, the product is effectively separated and purified by operations such as alkaline washing, extraction, drying, filtration, concentration and recrystallization to ensure that the final product has high chemical purity and isotopic abundance.
[0017] This invention also provides an aminopyrine prepared by the above method. 13 C2 compounds.
[0018] Alternatively, the aminopyrine- 13The structural formula of the C2 compound is as follows: .
[0019] The present invention also provides the above-mentioned aminopyrine- 13 The C2 compound is used to prepare reagents for drug metabolism studies or isotope tracers.
[0020] The present invention also provides the above-mentioned aminopyrine- 13 The purpose of C2 compounds is to prepare reagents for liver disease detection or liver disease grading.
[0021] All features disclosed in this specification, or all steps in all disclosed methods or processes, may be combined in any way, except for mutually exclusive features and / or steps.
[0022] Beneficial effects of this invention: This invention uses formic acid- 13 C is used as a carbon-13 labeling source, and this raw material can be used... 13 CO2 or 13 This method yields CH3OH through efficient conversion, and is widely available and inexpensive. Compared to existing technologies that use expensive or difficult-to-obtain isotopic reagents, this method significantly reduces the difficulty of raw material procurement and synthesis costs, while fully utilizing the high-abundance carbon-13 precursor, thus improving the economic efficiency of resource utilization.
[0023] The synthesis method described in this invention is carried out under mild conditions at 60°C, avoiding harsh reaction environments such as high temperature and high pressure, reducing the requirements for equipment tolerance, and also lowering the safety risks during operation. Compared with the strong reducing conditions or multi-step protection strategies commonly found in traditional methods, this scheme simplifies the process flow and improves the safety and controllability of the reaction.
[0024] This invention achieves direct two-site isotopic labeling of 4-aminoantipyrine through the synergistic effect of a platinum catalyst and triphenylsilane, efficiently introducing two carbon-13 atoms in a single step. This process is highly atom-economical, produces few byproducts, requires no intermediate separation, and significantly improves synthesis efficiency and resource utilization.
[0025] The catalytic system used in this invention consists of tetra(triphenylphosphine)platinum and 1,3-bis(diphenylphosphine)propane. The presence of the ligand enhances the stability and activity of the platinum catalyst, effectively inhibiting metal aggregation and deactivation. The addition of triphenylsilane as a mild reducing agent promotes the hydrogen transfer process, ensuring the selectivity and repeatability of the reaction and reducing the occurrence of side reactions.
[0026] The synthesis method described in this invention involves a homogeneous solution reaction, with each component exhibiting good solubility in dry dibutyl ether, ensuring sufficient contact and efficient mass transfer, which facilitates rapid and uniform reaction progression. Inert gas protection further maintains catalyst activity and system stability, improving batch-to-batch consistency.
[0027] The synthesis method described in this invention employs conventional extraction, alkali washing, drying, and recrystallization as post-processing steps. The process is simple, requiring no special purification equipment or complex separation methods, and is easy to implement at different production scales. The crude product can be recrystallized from n-hexane to obtain the high-purity target product. The method is highly adaptable and suitable for continuous and automated control.
[0028] The synthesis method described in this invention achieves a final product yield of 93%, significantly higher than similar isotope labeling methods reported in the literature, indicating that this route possesses excellent conversion efficiency and product recovery capability. The high yield reduces raw material waste and waste generation, aligning with green chemistry principles.
[0029] The synthesis method described in this invention can be completed in standard chemical equipment from starting materials to final purification. The reaction conditions are easy to replicate, the process parameters are clear, there is no violent exothermic reaction or dangerous intermediates, and it has good scalability characteristics, enabling a smooth transition to industrial production scale. Attached Figure Description
[0030] Figure 1 Aminopyrine - in some embodiments of the present invention 13 Synthetic route diagram of C2 compounds.
[0031] Figure 2 Aminopyrine - in some embodiments of the present invention 13 The result of liquid chromatography-mass spectrometry (LCMS) detection of compound C2.
[0032] Figure 3 Aminopyrine - in some embodiments of the present invention 13 Graph of high performance liquid chromatography (HPLC) detection results for C2 compound.
[0033] Figure 4 Aminopyrine - in some embodiments of the present invention 13 Quantitative nuclear magnetic resonance (QNMR) spectrum of C2 compound.
[0034] Figure 5 Aminopyrine - in some embodiments of the present invention 13 The hydrogen nuclear magnetic resonance (1H NMR) spectrum of the C2 compound in deuterated DMSO solvent.
[0035] Figure 6 Aminopyrine - in some embodiments of the present invention 13Carbon NMR (13C NMR) spectrum of C2 compound.
[0036] Figure 7 This is the carbon NMR spectrum of unlabeled aminopyrine.
[0037] Figure 8 Aminopyrine - in some embodiments of the present invention 13 Mass spectrum of C2 compound. Detailed Implementation
[0038] The following detailed description of specific embodiments further illustrates the above-described content of the present invention. However, this should not be construed as limiting the scope of the subject matter of the present invention to the following examples. Any modifications made without departing from the spirit and principles of the present invention, as well as equivalent substitutions or improvements made based on ordinary technical knowledge and common practice in the art, should be included within the scope of protection of the present invention.
[0039] Example 1: This application provides an aminopyrine- 13 Methods for synthesizing C2.
[0040] This method has significant advantages over the closest existing technologies (such as synthetic routes using multi-step reactions or high-valence isotope reagents), enabling the dual-site carbon-13 labeling of 4-aminoantipyrine through a one-step catalytic reduction reaction under mild conditions. It avoids complex protecting group operations and high-temperature and high-pressure conditions, greatly improving atom economy and process scalability.
[0041] Under argon protection, 2.1 g (5 mmol) of 1,3-bis(diphenylphosphine)propane was added to a dry reaction flask, followed by the addition of dry dibutyl ether (1 L), and the mixture was stirred until the ligand was completely dissolved.
[0042] Add 6.5 g (5 mmol) of tetra(triphenylphosphine)platinum catalyst and continue stirring until a uniform, slightly yellow solution is formed.
[0043] Maintain an argon atmosphere and stir the mixture for 10 minutes to ensure that the catalyst and ligands are fully coordinated.
[0044] When triphenylsilane (651 g, 2.5 mol) was added to the system, the solution color gradually changed from slightly yellow to colorless, indicating that the catalyst was effectively activated.
[0045] Immediately add 4-aminoantipyrine (101.62 g, 0.5 mol) and formic acid to the reaction system. 13 C (70.55 g, 1.5 mol), obvious bubbles were observed during the feeding process, indicating the initiation of decarboxylation and reduction reactions.
[0046] The reaction mixture was transferred to a constant-temperature oil bath and stirred continuously at 60°C for 18 hours. The reaction progress was monitored by LCMS sampling until the starting material was completely converted, thus completing the carbon-13 labeling reduction conversion process. Results are as follows: Figure 2 As shown, the main peak retention time is approximately 1.68 minutes, with singlets at 214 nm and 254 nm on DAD1, and peak areas of 2810.58 and 3104.59 mAU*s, respectively. Mass spectrometry shows a strong signal (area 2.58e6) at m / z 234 (EIC) for the parent ion, confirming the target analyte aminopyrine- 13 C2 exists and is of high purity.
[0047] After the reaction was completed, ethyl acetate (1.5 liters) was added to the reaction solution to dilute it, reduce the viscosity of the system and promote subsequent phase separation.
[0048] Slowly add 500 mL of 3 M NaOH aqueous solution, controlling the dropping rate to avoid violent exothermic reactions. After the addition is complete, stir vigorously at room temperature for 3 hours to completely decompose the residual reagent and neutralize the acidic byproducts.
[0049] Transfer the reaction mixture to a separatory funnel and extract with ethyl acetate three times, using 500 mL each time. Combine all organic phases.
[0050] The combined organic layer was dried with anhydrous magnesium sulfate and stirred for 30 minutes until the solution was clear and no obvious water was present.
[0051] Remove the desiccant by filtering through filter paper or a glass frit funnel, and collect the filtrate.
[0052] The filtrate was concentrated under reduced pressure in a rotary evaporator to remove the solvent, yielding a yellow, oily crude product.
[0053] The crude product was purified using n-hexane as a recrystallization solvent. After heating to dissolve, it was slowly cooled to room temperature, and white crystals precipitated.
[0054] The crystals were collected by filtration, washed with a small amount of cold n-hexane, and dried under vacuum to obtain pure aminopyrine. 13 C2 (108.5 g, yield 93%).
[0055] Figure 3The high-performance liquid chromatography (HPLC) results of the product are shown, using an XBridge C18 column at a wavelength of 214 nm and a column temperature of 35°C. A single peak appeared at a retention time of approximately 7.252 minutes, with a peak area of 112.154 mAU*min, a peak height of 1320.214 mAU, and an area percentage of 100.00%. The total peak area was 100%, and no other impurity peaks were observed, indicating that the sample is a single component with extremely high purity. The blank control (BLANK) showed no peaks, eliminating background interference. Figure 4 As shown, the characteristic proton peaks of the product are clear, and the chemical shifts and integral values are similar to those of aminopyrine- 13 The C2 structure is consistent. The spectral peaks have stable baselines, with no obvious impurity interference peaks, and the integration results are accurate and reliable. Figure 5 As shown, the chemical formula of the target compound is C 11 13 C2H 17 N3O, precise molecular weight 233.14. In the spectrum, the aromatic region (7.25-7.48 ppm) has an integral of approximately 2.03, corresponding to the signals of three protons on the benzene ring; the high-field regions at 3.04 ppm (integral approximately 6.23) and 2.18 ppm represent the proton signals of N-methyl and 13C-labeled dimethyl groups, respectively; the solvent peak (DMSO-d6) is located around 2.50 ppm. The peaks are clearly assigned, and the integral ratios are consistent with the structure, with no obvious impurity interference, indicating that the sample structure is correct and of high purity. Figure 6 As shown, two enhanced methyl carbon signals should be observable in the chemical shift range of approximately 40-45 ppm (corresponding to...). 13 CH3), confirming N,N-dimethyl- 13 The presence of C2 labeling was also observed. Furthermore, signals from the carbonyl carbon (approximately 170-175 ppm) and aromatic carbon (approximately 120-150 ppm) matched well with the Aminopyrine structure. The carbon signals were clearly assigned, with no obvious impurities or label loss, indicating that the 13C-labeled compound has a correct structure and high isotopic purity. Figure 8 As shown, the aminopyrine-13C2 precursor ion is 234, with a corresponding mass spectral area integral of 2583410; the aminopyrine-13C precursor ion is 233, with a corresponding mass spectral area integral of 62992.3; the unlabeled aminopyrine precursor ion is 232, and no corresponding mass spectral information is obtained from LCMS. Based on the proportion of mass spectral area integrals, the proportions of isotopic abundance are as follows: 13 C2: 97.62%; 13 C1: 2.38%. The abundance of the isotope is: (97.62%*2+2.38%*1) / 2=98.81%.
[0056] Example 2: The aminopyrine provided in the embodiments of this application -13 The synthesis method for C2 is also applicable to reaction conditions with larger feed scales and has good scalability.
[0057] This method, while maintaining the same catalyst system and reaction temperature, can scale up the dosage of each component proportionally and still maintain high yield and good reaction control, making it suitable for industrial production needs.
[0058] Under argon protection, 42 g of 1,3-bis(diphenylphosphine)propane was dissolved in 20 L of dry dibutyl ether and stirred until completely dissolved.
[0059] Add 130 g of tetra(triphenylphosphine)platinum catalyst (100 mmol) and stir to form a slightly yellow transparent solution.
[0060] After stirring for 10 minutes, add triphenylsilane (13020 g, 50 mol). The solution color changes from slightly yellow to colorless, confirming that the catalyst activation is complete.
[0061] Quickly add 4-aminoantipyrine (2032.4 g, 10 mol) and formic acid- 13 C (1411 g, 30 mol) was observed to release continuous bubbles during the addition of the material, indicating that the reaction started immediately.
[0062] The reaction mixture was stirred at a constant temperature of 60°C for 18 hours, and the reaction was periodically monitored using LCMS to confirm its completeness.
[0063] After the reaction is complete, add ethyl acetate (30 liters) to dilute the reaction solution.
[0064] Slowly add 10 liters of 3 M NaOH aqueous solution and stir vigorously at room temperature for 3 hours to ensure that any remaining reactants are fully quenched.
[0065] The mixture was extracted with ethyl acetate, 5 liters each time, repeated three times, and all organic phases were combined.
[0066] The combined organic layer was dried with anhydrous magnesium sulfate for 30 minutes with gentle stirring.
[0067] The desiccant was removed by filtration, and the filtrate was collected and concentrated under reduced pressure to remove the solvent and obtain the crude product.
[0068] The crude product was recrystallized in hexane as a solvent, dissolved by heating, and then naturally cooled to crystallize.
[0069] The mixture is filtered, washed, and vacuum dried to obtain aminopyrine. 13 C2 (2077 g, 89% yield), the structure and isotopic abundance of the product were confirmed by mass spectrometry analysis.
[0070] Example 3: Under a protective atmosphere in which nitrogen was used instead of argon, 2.1 g of 1,3-bis(diphenylphosphine)propane was dissolved in 1 L of dry dibutyl ether.
[0071] Add 6.5 g (5 mmol) of tetra(triphenylphosphine)platinum catalyst and stir to form a slightly yellow solution.
[0072] After stirring for 10 minutes, triphenylsilane (651 g, 2.5 mol) was added. The solution gradually turned colorless, indicating that the catalytic system had been activated.
[0073] Immediately add 4-aminoantipyrine (101.62 g, 0.5 mol) and formic acid- 13 C (70.55 g, 1.5 mol), the reaction system immediately produces bubbles.
[0074] The reaction mixture was stirred at 60°C for 18 hours, and the reaction was confirmed to be complete by LCMS.
[0075] Dilute the reaction solution with ethyl acetate (1.5 liters).
[0076] Slowly add 500 ml of 3 M NaOH aqueous solution and stir vigorously at room temperature for 3 hours to complete the treatment.
[0077] Extract three times with ethyl acetate (500 mL each time), and combine the organic phases.
[0078] The combined organic phases were dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product.
[0079] The crude product was recrystallized from n-hexane. After the crystals precipitated, the mixture was filtered, washed, and dried to obtain aminopyrine- 13 C2 (106.8 g, yield 91.4%), slightly lower than under argon conditions but still maintaining a high yield level.
[0080] Example 4: The aminopyrine provided in the embodiments of this application - 13 In the synthesis of C2, formic acid- 13 Adding C in batches helps to improve local concentration fluctuations in the reaction system and enhance reaction uniformity and mass transfer efficiency.
[0081] By controlling formic acid- 13 The timing of adding C can effectively alleviate the problem of violent instantaneous venting caused by a single feeding, enhance the controllability of the reaction, and reduce the risk of side reactions.
[0082] 1,3-bis(diphenylphosphine)propane (2.1 g, 5 mmol) and tetra(triphenylphosphine)platinum catalyst (6.5 g, 5 mmol) were added together to dry dibutyl ether (1 L) and stirred under argon protection to form a slightly yellow solution.
[0083] After stirring for 10 minutes, add triphenylsilane (651 g, 2.5 mol), and the solution becomes colorless.
[0084] Add 101.62 g (0.5 mol) of 4-aminoantipyrine and formic acid respectively. 13 C (70.55 g, 1.5 mol), of which formic acid- 13 C is added in batches, with one-third of the total amount added every 10 minutes, for a total of three additions. Bubbles are continuously observed to form during the addition process.
[0085] The reaction mixture was stirred at 60°C for 18 hours, and LCMS analysis showed that the reaction was complete.
[0086] The subsequent processing steps are the same as in Example 1: add ethyl acetate (1.5 L) to dilute, slowly add 3 M NaOH aqueous solution (500 mL), and stir vigorously at room temperature for 3 hours.
[0087] Extracted three times with ethyl acetate, the organic phases were combined and dried over anhydrous magnesium sulfate.
[0088] After filtration and concentration, the crude product was obtained, and then recrystallized from n-hexane to obtain aminopyrine- 13 C2 (107.2 g, yield 92.1%) indicates that batch feeding helps improve local concentration fluctuations and enhance reaction uniformity.
[0089] The above description is merely a preferred embodiment of the present invention and is illustrative rather than restrictive. Those skilled in the art will understand that many changes, modifications, and even equivalent alterations can be made within the spirit and scope defined by the claims of the present invention, but all such changes will fall within the protection scope of the present invention.
Claims
1. An aminopyrine- 13 The method for synthesizing C2 compounds is characterized by, two of the carbon atoms in the compound are carbon-13 isotopically labeled, and the carbon-13 atoms are derived from formic acid 13 C.
2. The synthesis method according to claim 1, characterized in that, A catalytic system consisting of a platinum catalyst and a bidentate phosphine ligand, using triphenylsilane as a reducing agent, is employed to react formic acid- 13 The carbon-13 atom in C is introduced into the 4-aminoantipyrine molecule to achieve aminopyrine- 13 Synthesis of C2.
3. The synthesis method according to claim 1, characterized in that, Specifically, the following steps are included: Under inert gas protection, 4-aminoantipyrine and formic acid- 13 C is mixed in a solvent; a catalytic system is formed by adding a platinum catalyst and ligands; simultaneously, triphenylsilane is added as a reducing agent to make formic acid- 13 The carbon-13 atom in C is introduced into the 4-aminoantipyrine molecule via a catalytic reduction reaction, generating aminopyrine- 13 C2.
4. The synthesis method according to claim 3, characterized in that, The ligand is a bidentate phosphine ligand, preferably 1,3-bis(diphenylphosphine)propane.
5. The synthesis method according to claim 3, characterized in that, The solvent is a dry ether solvent, preferably dibutyl ether.
6. The synthesis method according to claim 3, characterized in that, The reaction temperature is 50℃~80℃, preferably 60℃.
7. The synthesis method according to claim 3, characterized in that, The reaction time is 12 to 24 hours.
8. The synthesis method according to claim 3, characterized in that, Formic acid- 13 C is added to the reaction system in batches.
9. An aminopyrine prepared by any one of the methods described in claims 1-8 13 C2 compounds.
10. An aminopyrine as described in claim 9 13 The uses of C2 compounds, characterized in that It is used to prepare reagents for drug metabolism research or isotope tracer reagents.