TW202328077A - Hydrogenation synthesis method for preparing pyrazinecarboxylic acid derivative as fluorescent tracer - Google Patents

Abstract

Provided is a hydrogenation synthesis method for preparing a pyrazinecarboxylic acid derivative as a fluorescent tracer, in particular, provided is a method for preparing 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine. According to the method, flammable and explosive hydrogen is prevented from being used, the problem of blocking of a pipeline caused by sublimation of ammonium for mate is solved, and safety hazards in production is greatly reduced.

Description

Hydrogenation synthesis method for preparing pyrazine carboxylic acid derivatives as fluorescent tracers

The present invention relates to the preparation of 3,6-diamino-2,5-bis{N-[(1R)-1-carboxylic acid-2-hydroxyethyl] for use as a fluorescent tracer in medical diagnosis The carbamoyl}pyrazine method.

Pyrazine derivatives have potential applications as fluorescent tracers in the assessment of renal function. As a fluorescent tracer with great clinical application value, 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]aminoformyl The research on }pyrazine (hereinafter also referred to as "compound of formula 1" or "compound 1") has received extensive attention, but there are very few reports on the synthesis route of this compound.

In 2011, Raghavan Rajagopalan et al. optimized the synthesis of compound 1 and reduced the number of reaction steps (J. Med. Chem., 2011, 54, 5048-5058). In this synthesis method, 3,6-diaminopyrazine-2,5-dicarboxylic acid as a raw material is subjected to amidation, palladium-catalyzed hydrogenation and other steps to obtain compound 1: However, the second step of this route uses hydrogen as the hydrogen source, which not only requires pressurization but also takes a long time to react in industrial production; moreover, hydrogen is a flammable and explosive gas, which poses a great safety hazard in industrial production.

Therefore, there is still a need to develop a suitable 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl group with high safety and high efficiency. } The industrial production method of pyrazine.

The purpose of the present invention is to overcome the problems existing in the prior art, avoid the use of inflammable and explosive hydrogen, and reduce the potential safety hazards in industrial production.

A further object of the present invention is to shorten the reaction time while realizing the yield and quality of compound 1 equivalent to those of the prior art (such as Raghavan Rajagopalan et al., J. Med. Chem. , 2011, 54, 5048-5058.) . This is of great significance for industrial production.

The above object is achieved by providing a preparation method suitable for the industrial production of Compound 1 of the present invention.

In general, the present invention provides a method for the preparation of 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl } A new method for pyrazine (hereinafter also referred to as "compound 1"), said method comprising the following steps: A compound of formula 5 (hereinafter also referred to as "compound 5") is reacted with a hydrogen-borrowing reagent in a solvent in the presence of a suitable metal catalyst to provide the 3,6-diamine group of formula 1 -2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]aminoformyl}pyrazine, wherein the solvent is selected from alcohol or alcohol aqueous solution.

definition

Unless defined otherwise hereinafter, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. References to techniques used herein are intended to refer to techniques commonly understood in the art, including those variations of the techniques or substitutions of equivalent techniques that are obvious to those skilled in the art. While the following terms are believed to be well understood by those skilled in the art, the following definitions are set forth to better explain the present invention.

As used herein, the terms "comprises," "comprising," "has," "containing," or "involving," and other variations thereof herein, are inclusive or open-ended, and do not Other unrecited elements or method steps are excluded although other unrecited elements or method steps are not necessarily present (ie, these terms also encompass the terms "consisting essentially of" and "consisting of").

As used herein, the term "hydrogen borrowing reaction", also known as a hydrogen transfer reaction, refers to the use of a metal catalyst to dehydrogenate a relatively inert organic compound to form a metal hydride while simultaneously activating the organic compound and participating in a subsequent reaction An intermediate is formed, which is then reduced by the metal hydride to form a new product. Such organic compounds are referred to as "hydrogen borrowing agents".

As used herein, the term "room temperature" refers to about 20 to 25°C.

The term "about" means within ±10%, preferably within ±5%, more preferably within ±2% of the stated value.

In a first aspect, the present invention provides for the preparation of 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyridine The method for oxazine, is characterized in that, described method comprises the following steps: A compound of formula 5 is subjected to a hydrogen borrowing reaction with a hydrogen borrowing reagent in a solvent in the presence of a suitable metal catalyst to provide the 3,6-diamino-2,5-bis{N-[( 1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine, wherein the solvent includes alcohol or an aqueous alcohol solution.

The hydrogen-borrowing reagent used in the method of the present invention is preferably a reagent suitable for industrial production. The use of certain reagents may pose production hazards and is therefore not preferred. For example, ammonium formate is prone to sublimation, which can cause clogging problems.

In some embodiments, the hydrogen-borrowing agent is selected from a combination of formic acid and an alkali metal formate, cyclohexadiene, and isopropanol.

In some embodiments, the molar ratio of the compound of formula 5 to the hydrogen-borrowing agent is about 1:2 to 1:20, preferably about 1:2 to 1:10, such as about 1:2.5, about 1:4, about 1:5, about 1:6, or about 1:8.

In some embodiments, the metal catalyst is palladium on carbon (Pd/C). The mass fraction of palladium in the Pd/C catalyst can be about 5 to 20%, preferably about 10%. For example, the Pd/C catalyst may contain about 50 w/w% water.

In some embodiments, the mass ratio of the compound of formula 5 to the metal catalyst is about 10:1 to 10:3, preferably about 10:2.

In some embodiments, the solvent is alcohol.

In other embodiments, the solvent is an aqueous alcohol solution. The volume ratio of alcohol to water in the alcohol aqueous solution may be about 1:10 to 10:1, preferably about 1:8 to 8:1, more preferably about 4:1 to 8:1.

In some of the above-described embodiments, whether the solvent includes water or not, the amount of the alcohol may be about 4 to 40 times (v/w) the amount of the compound of formula 5, such as about 10, 15, 25, 30 or 35 times (v/w).

The alcohol can be selected from methanol, ethanol, isopropanol and mixtures thereof, preferably methanol or ethanol, more preferably ethanol.

In some embodiments, the hydrogen borrowing reaction is carried out at a temperature of about 20°C to 100°C, preferably about 20°C to 80°C. In some preferred embodiments, the hydrogen borrowing reaction is performed at a temperature of about 50°C to 70°C. In some preferred embodiments, the hydrogen borrowing reaction is performed at room temperature.

In some embodiments, the hydrogen borrowing reaction is carried out for about 1 to 12 hours, preferably about 2 to 12 hours, more preferably about 2 hours, 10 hours or 12 hours, to complete the conversion of the compound of formula 5 to the formula 1. Transformation of Compounds.

In some preferred embodiments, the hydrogen borrowing reaction is carried out at a temperature of about 70° C. for about 2 hours to complete the conversion of the compound of formula 5 to the compound of formula 1.

The conversion to the compound of formula 1 can be monitored by detecting the residual amount of the compound of formula 5 in the reactant, eg, by thin layer chromatography (TLC).

The compound of formula 1 generated can be separated and purified by the following steps: (1) After the hydrogen borrowing reaction is completed, filter the reaction mixture, and wash the filter cake with an aqueous alcohol solution until the filtrate is light yellow, and combine the obtained filtrate; (2) concentrating the filtrate to obtain the crude product of the compound of formula I; (3) adding an appropriate amount of acetonitrile or water to the crude product of the compound of formula I and beating for a suitable time (for example, about 1 to 4 hours); (4) filtering, and drying the filter cake under reduced pressure at a suitable temperature (for example, about 40 to 45°C) to obtain the compound of formula I.

The aqueous alcohol solution described in step (1) may be, for example, an aqueous ethanol solution. The water content of the aqueous ethanol solution may be about 25% to 40% (v/v), preferably about 30% to 36% (v/v).

In a second aspect, the present invention provides the method as described in the first aspect above, wherein the hydrogen-borrowing reagent is a combination of formic acid and alkali metal formate.

In some embodiments, the molar ratio of the formic acid to the alkali metal formate is about 1:6 to 6:1, preferably about 1:1 to 5:1, more preferably about 1:2 to 5 :1.

In some embodiments, the molar ratio of the compound of formula 5 to the sum of the formic acid and the alkali metal formate is about 1:2 to 1:20, such as about 1:4 to 1:18, About 1:6 to 1:16 or about 1:8 to 1:12. In some preferred embodiments, the molar ratio is about 1:5 to 1:10, such as about 1:6 to 1:8, more preferably about 1:6.

In some preferred embodiments, the alkali metal formate is sodium formate or potassium formate, preferably potassium formate.

The combination of formic acid and alkali metal formate can be obtained by adding separate formic acid and alkali metal formate or a mixture thereof to the reaction system, or by adding an appropriate amount of formic acid and an appropriate amount of the corresponding alkali metal base in the reaction system. reaction to form in situ. The base may be selected from potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate and sodium bicarbonate and any combination thereof.

In some preferred embodiments, the solvent is an aqueous alcohol solution. The volume ratio of alcohol to water in the alcohol aqueous solution may be about 1:10 to 10:1, preferably about 1:8 to 8:1, more preferably about 4:1 to 8:1. The amount of said alcohol can be about 10 to 40 times (v/w), preferably about 10 to 35 times (v/w), such as 15, 25 or 30 times (v/w) of the amount of the compound of formula 5 w). In some preferred embodiments, the alcohol is selected from methanol, ethanol and mixtures thereof, preferably methanol or ethanol, more preferably ethanol.

In some embodiments, the hydrogen borrowing reaction is performed at a temperature of about 50°C to 80°C, preferably at about 50°C, about 60°C or more preferably about 70°C.

In some embodiments, the hydrogen borrowing reaction is performed for about 2 to 12 hours, preferably about 2 hours, to complete the conversion of the compound of formula 5 to the compound of formula 1.

The method can achieve the same yield and quality of compound 1 as reported by Raghavan Rajagopalan et al. (J. Med. Chem., 2011, 54, 5048-5058).

In some more preferred embodiments, the hydrogen borrowing reaction is performed at a temperature of about 70° C. for about 2 hours to complete the conversion of the compound of formula 5 to the compound of formula 1.

In some particularly preferred embodiments, the present invention provides a method as described above, wherein the hydrogen-borrowing reagent is a combination of formic acid and potassium formate in a molar ratio of about 1:2 to 5:1; The molar ratio of the compound of the formula 5 to the sum of the formic acid and the potassium formate is about 1:5 to 1:10, more preferably about 1:6; The solvent is an aqueous solution of methanol or ethanol, wherein the volume ratio of the methanol or ethanol to water is about 4:1 to 8:1; The amount of methanol or ethanol is about 15 to 35 times (v/w) that of the compound of formula 5; The metal catalyst is Pd/C, wherein the mass fraction of palladium in the Pd/C catalyst is about 10% (for example, the Pd/C catalyst contains about 50 w/w% water); The mass ratio of the compound of the formula 5 to the Pd/C catalyst is about 10:2; and The hydrogen borrowing reaction is carried out at a temperature of about 50°C to 70°C for about 2 to 12 hours, more preferably at a temperature of about 70°C for about 2 hours, to complete the conversion of the compound of the formula 5 to the formula 1. Transformation of Compounds.

The resulting compound of formula 1 can be isolated and purified by the steps described in the first aspect above. In some embodiments, the isolation and purification process may also include adding an appropriate amount of acid (e.g., the same molar amount of alkali metal base used to form the alkali metal formate in situ) to the combined filtrate and Mixing steps. For example, when the combination of formic acid and alkali metal formate is formed in situ as described above, the same molar amount of alkali metal base used to form the alkali metal formate in situ can be added to the combined filtrate. amount of acid. The acid is preferably hydrochloric acid. Then, the resulting mixture was concentrated to obtain the crude compound of formula I.

In a third aspect, the present invention provides the method as described in the first aspect above, wherein the hydrogen-borrowing reagent is cyclohexadiene.

In some embodiments, the molar ratio of the compound of formula 5 to the cyclohexadiene is about 1:2 to 1:5; preferably about 1:2 to 1:3.

In some embodiments, the solvent is alcohol, preferably methanol or ethanol, more preferably ethanol.

In some embodiments, the amount of the alcohol is about 4 to 10 times (v/w), such as about 4, about 6 or about 8 times (v/w) the amount of the compound of formula 5.

In some embodiments, the hydrogen borrowing reaction is performed at room temperature for about 10 to 12 hours to complete the conversion of the compound of Formula 5 to the compound of Formula 1 .

In some embodiments, the present invention provides a method as described above, wherein the hydrogen-borrowing reagent is cyclohexadiene; The molar ratio of the compound of the formula 5 to the cyclohexadiene is about 1:2 to 1:3; The solvent is methanol or ethanol, and the amount of the methanol or ethanol is about 4 to 6 times (v/w) the amount of the compound of formula 5; The metal catalyst is Pd/C, wherein the mass fraction of palladium in the Pd/C catalyst is about 10% (for example, the Pd/C catalyst contains about 50 w/w% water); The mass ratio of the compound of the formula 5 to the Pd/C catalyst is about 10:2; and The hydrogen borrowing reaction is carried out at room temperature for about 10 to 12 hours to complete the conversion of the compound of formula 5 to the compound of formula 1.

The resulting compound of formula 1 can be isolated and purified by the steps described in the first aspect above.

Beneficial effect

The method of the invention avoids the use of inflammable and explosive hydrogen, and greatly reduces potential safety hazards in industrialized production. The method of the present invention also has the advantages that the debenzylation reaction is carried out completely and there is basically no side reaction. Moreover, by adjusting the reaction conditions (for example, the ratio of reactants and reaction temperature), the method of the present invention is equivalent to that reported by Raghavan Rajagopalan et al. (J. Med. Chem., 2011, 54, 5048-5058). While improving the yield and quality of compound 1, the reaction time can be shortened from more than 10 hours reported by Raghavan Rajagopalan et al. to about 2 hours or less, thereby greatly shortening the production time. The method of the present invention also avoids the problem of clogged lines caused by sublimation when ammonium formate is used. The method of the invention has low requirements on equipment, simple and convenient operation, high yield, high safety and cost-effectiveness, is suitable for industrial production, and has important application value.

Example

The present invention is further described below in conjunction with examples, but these examples are not intended to limit the scope of the present invention.

The experimental method that does not indicate specific condition in the embodiment of the present invention, is conventional condition usually, or according to the condition suggested by raw material or commodity manufacturer; Known reagents are prepared by conventional methods.

Reagents and instruments 1. HRMS instrument model: Agilent 1290 Q-TOF-6545A; Reagents: formic acid, trifluoroacetic acid, acetonitrile, methanol. 2. LC/MS instruments: Waters 2767 Sample Manager, Waters 515 HPLC Pump, Waters2489UV/Visible Detector, Waters 3100 Mass Detector; Reagents: purified water, acetonitrile. The mass spectrum is measured by LC-MS instrument, and the ionization method can be ESI or APCI. Thin layer chromatography (TLC) used Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plate. The size of the silica gel plate used is 0.15 mm to 0.2 mm, and the size of the silica gel plate used for thin layer chromatography separation and purification is 0.4 mm to 0.5 mm. Column chromatography generally uses Yantai Huanghai 200-300 mesh silica gel as the carrier. Various starting materials and reagents were either commercially available or synthesized according to known methods, and commercially available materials and reagents were used without further purification unless otherwise indicated.

Embodiment 1 : Preparation of 3,6- diamino -2,5- bis {N-[(1R)-1- carboxy -2- hydroxyethyl ] aminoformyl } pyrazine into 250 mL reaction flask 20 mL of purified water and 0.56 g KOH were added to the solution, and after complete dissolution, 2.76 g of HCOOH and 80 mL of ethanol were added. After stirring for 5 min, 5.00 g of compound 5 and 1 g of 10% Pd/C (50% water content) were added at room temperature. Heating to reflux at 70 °C for 2 h, TLC monitoring showed that the reaction was complete, and the Pd/C was filtered out with diatomaceous earth while it was still hot. The filter cake was washed with ethanol aqueous solution (30% H ₂ O, V/V) until the filtrate was light yellow, and the filtrates were combined. Add 10 ml of 1N hydrochloric acid to the filtrate, stir for 15 min and concentrate to dryness under reduced pressure. The resulting solid was slurried with 50 mL of acetonitrile/water for 2 h, then filtered. The filter cake was dried under reduced pressure at 40° C. for 12 h to obtain 2.19 g of the title compound as a solid (molar yield: 65%). LC-MS: RT=3.02 min, [MH]=370.9. HRMS: [M+H ⁺ ]=373.1110. ¹ H NMR [500Hz, DMSO- d6 ] δ 8.47 (d, 2H), 6.78 (s, 4H) , 4.47 (dt, 2H), 3.90 (dd, 2H), 3.76 (dd, 2H).

Comparative Example 1 : The preparation of 3,6- diamino -2,5- bis {N-[(1R)-1- carboxy -2- hydroxyethyl ] aminoformyl } pyrazine except without adding KOH , repeat the operation of embodiment 1. Specifically, 20 mL of purified water was added to a 250 mL reaction flask, followed by 2.76 g of HCOOH and 80 mL of ethanol. After stirring for 5 min, 5.00 g of compound 5 and 1 g of 10% Pd/C (50% water content ), heated to reflux at 70 °C for 2 h. TLC monitoring showed that the target compound was almost invisible, and there was a large amount of residue at the raw material point.

Embodiment 2 : Preparation of 3,6- diamino -2,5- bis {N-[(1R)-1- carboxy -2- hydroxyethyl ] aminoformyl } pyrazine into a 250mL reaction flask 20 mL of purified water and 2.23 g of KOH were added, and after complete dissolution, 2.76 g of HCOOH and 160 mL of ethanol were added. After stirring for 5 min, 5.00 g of compound 5 and 1 g of 10% Pd/C (50% water content) were added at room temperature. Heating to reflux at 60°C for 10 h, TLC monitoring showed that the reaction was complete, and the Pd/C was filtered out with diatomaceous earth while it was still hot. The filter cake was washed with ethanol aqueous solution (30% H ₂ O, V/V) until the filtrate was light yellow, and the filtrates were combined. Add 40 ml of 1N hydrochloric acid to the filtrate, stir for 15 min and concentrate to dryness under reduced pressure. The resulting solid was slurried with 30 mL of water for 2 h, then filtered. The filter cake was dried under reduced pressure at 40°C for 12 h to obtain 2.12 g of the title compound as a solid (molar yield: 63%). LC-MS: RT=3.02min, [MH]=370.9. HRMS and ¹ H NMR data are the same as in Example 1.

Embodiment 3 : Preparation of 3,6- diamino -2,5- bis {N-[(1R)-1- carboxy -2- hydroxyethyl ] aminoformyl } pyrazine into 250 mL reaction flask 20 mL of purified water and 2.23 g of KOH were added to it, and after complete dissolution, 2.76 g of HCOOH and 80 mL of methanol were added. After stirring for 5 min, 5.00 g of compound 5 and 1 g of 10% Pd/C (50% water content) were added at room temperature. Heated to reflux at 50°C for 12 h, TLC monitoring showed that the reaction was complete, and the Pd/C was filtered out with diatomaceous earth while it was still hot. The filter cake was washed with ethanol aqueous solution (36% H ₂ O, V/V) until the filtrate was light yellow, and the filtrates were combined. Add 40 ml of 1N hydrochloric acid to the filtrate, stir for 15 min, concentrate under reduced pressure to 25 mL, and then filter. The filter cake was slurried with 50 mL of water for 2 h, and then filtered. The filter cake was dried under reduced pressure at 40°C for 12 h to obtain 1.85 g of the title compound as a red solid (molar yield: 55%). LC-MS: RT=3.02min, [MH]=370.9. HRMS and ¹ H NMR data are the same as in Example 1.

Embodiment 4 : Preparation of 3,6- diamino -2,5- bis {N-[(1R)-1- carboxy -2- hydroxyethyl ] aminoformyl } pyrazine into 250 mL reaction flask Add 20 mL of ethanol and 5.00 g of compound 5, 2 g of cyclohexadiene and 1 g of 10% Pd/C (water content 50%), react at room temperature for 12 h, TLC monitoring shows that the reaction is complete, filter through diatomaceous earth Except Pd/C. The filter cake was washed with ethanol aqueous solution (36% H ₂ O, V/V) until the filtrate was light yellow, and the filtrates were combined. The filtrate was concentrated to dryness, slurried with 20 mL of water for 2 h, and then filtered. The filter cake was dried under reduced pressure at 40°C for 12 h to obtain 2.20 g of the title compound as a red solid (molar yield: 65%). LC-MS: RT=3.02 min, [MH]=370.9. HRMS and ¹ H NMR data are the same as in Example 1.

In addition to the embodiments described herein, various modifications of the invention will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

Each reference cited in this application, including all patents, patent applications, journal articles, books, and any other publications, is hereby incorporated by reference in its entirety.

Claims (18)

A method for preparing 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]aminoformyl}pyrazine of formula 1, characterized in that , the method includes the following steps: A compound of formula 5 is subjected to a hydrogen borrowing reaction with a hydrogen borrowing reagent in a solvent in the presence of a suitable metal catalyst to provide the 3,6-diamino-2,5-bis{N-[( 1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine, wherein the solvent includes alcohol or an aqueous alcohol solution. The method of claim 1, wherein the hydrogen-borrowing reagent is selected from a combination of formic acid and alkali metal formate, cyclohexadiene and isopropanol; and/or The molar ratio of the compound of formula 5 to the hydrogen-borrowing agent is about 1:2 to 1:20, preferably about 1:2 to 1:10, such as about 1:2.5, about 1:4, about 1 :5, about 1:6 or about 1:8. The method of claim 1 or 2, wherein the metal catalyst is palladium on carbon (Pd/C); Preferably, the mass fraction of palladium in the Pd/C catalyst is about 5 to 20%, preferably about 10% (for example, the Pd/C catalyst contains about 50 w/w% water). The method according to any one of claims 1 to 3, characterized in that the mass ratio of the compound of formula 5 to the metal catalyst is about 10:1 to 10:3, preferably about 10:2. The method according to any one of claims 1 to 4, wherein the solvent is alcohol. The method according to any one of claims 1 to 4, wherein the solvent is an aqueous alcohol solution; Preferably, the volume ratio of alcohol to water in the aqueous alcohol solution is about 1:10 to 10:1, more preferably about 1:8 to 8:1, more preferably about 4:1 to 8:1. The method according to any one of claims 5 to 7, wherein the amount of the alcohol is about 4 to 40 times (v/w) the amount of the compound of the formula 5, such as about 10, 15, 25 , 30 or 35 times (v/w). The method according to any one of claims 5 to 7, wherein the alcohol is selected from methanol, ethanol, isopropanol and mixtures thereof, preferably methanol or ethanol, more preferably ethanol. The method according to any one of claims 1 to 8, characterized in that, the hydrogen-borrowing reaction is carried out at about 20°C to 100°C, preferably at about 20°C to 80°C, more preferably at room temperature or at about 50°C °C to 70°C; and/or The hydrogen borrowing reaction is carried out for about 1 to 12 hours, preferably about 2 to 12 hours, more preferably about 2 hours, 10 hours or 12 hours, so as to complete the conversion of the compound of formula 5 to the compound of formula 1. The method according to any one of claims 1 to 9, wherein the hydrogen-borrowing reagent is a combination of formic acid and alkali metal formate; Preferably, the molar ratio of the formic acid to the alkali metal formate is about 1:6 to 6:1, preferably about 1:1 to 5:1, more preferably about 1:2 to 5:1 and/or Preferably, the molar ratio of the compound of the formula 5 to the sum of the formic acid and the alkali metal formate is about 1:2 to 1:20, preferably about 1:5 to 1:10, more preferably Canon 1:6. The method according to claim 10, wherein the alkali metal formate is sodium formate or potassium formate, preferably potassium formate. The method according to claim 10 or 11, wherein the solvent is an aqueous alcohol solution as defined in any one of claims 6 to 8; and/or The amount of the alcohol is about 10 to 40 times (v/w), preferably about 15 to 35 times (v/w) of the amount of the compound of formula 5, preferably, the alcohol is selected from methanol, Ethanol and mixtures thereof, preferably methanol or ethanol, more preferably ethanol. The method according to any one of claims 10 to 12, characterized in that the hydrogen-borrowing reaction is performed at about 50°C to 80°C, preferably at about 50°C, about 60°C or more preferably about 70°C at a temperature of C; and/or The hydrogen borrowing reaction is carried out for about 2 to 12 hours, preferably about 2 hours, to complete the conversion of the compound of formula 5 to the compound of formula 1; Preferably, the hydrogen borrowing reaction is carried out at a temperature of about 70° C. for about 2 hours to complete the conversion of the compound of formula 5 to the compound of formula 1. The method of claim 1, wherein the hydrogen-borrowing reagent is a combination of formic acid and potassium formate with a molar ratio of about 1:2 to 5:1; The molar ratio of the compound of the formula 5 to the sum of the formic acid and the potassium formate is about 1:5 to 1:10, more preferably about 1:6; The solvent is an aqueous solution of methanol or ethanol, wherein the volume ratio of the methanol or ethanol to water is about 4:1 to 8:1; The amount of methanol or ethanol is about 15 to 35 times (v/w) that of the compound of formula 5; The metal catalyst is Pd/C, wherein the mass fraction of palladium in the Pd/C catalyst is about 10% (for example, the Pd/C catalyst contains about 50 w/w% water); The mass ratio of the compound of the formula 5 to the Pd/C catalyst is about 10:2; and The hydrogen borrowing reaction is carried out at a temperature of about 50°C to 70°C for about 2 to 12 hours, more preferably at a temperature of about 70°C for about 2 hours, to complete the conversion of the compound of the formula 5 to the formula 1. Transformation of Compounds. The method according to any one of claims 1 to 9, wherein the hydrogen-borrowing reagent is cyclohexadiene; Preferably, the molar ratio of the compound of formula 5 to the cyclohexadiene is about 1:2 to 1:5; preferably about 1:2 to 1:3. The method according to claim 15, wherein the solvent is alcohol, preferably methanol or ethanol, more preferably ethanol; and/or The amount of the alcohol is about 4 to 10 times (v/w), such as about 4, about 6 or about 8 times (v/w) of the amount of the compound of formula 5. The method according to claim 15 or 16, wherein the hydrogen borrowing reaction is carried out at room temperature for about 10 to 12 hours to complete the conversion of the compound of formula 5 to the compound of formula 1. The method of claim 1, wherein the hydrogen-borrowing reagent is cyclohexadiene; The molar ratio of the compound of the formula 5 to the cyclohexadiene is about 1:2 to 1:3; The solvent is methanol or ethanol, and the amount of the methanol or ethanol is about 4 to 6 times (v/w) the amount of the compound of formula 5; The metal catalyst is Pd/C, wherein the mass fraction of palladium in the Pd/C catalyst is about 10% (for example, the Pd/C catalyst contains about 50 w/w% water); The mass ratio of the compound of the formula 5 to the Pd/C catalyst is about 10:2; and The hydrogen borrowing reaction is carried out at room temperature for about 10 to 12 hours to complete the conversion of the compound of formula 5 to the compound of formula 1.