CN114524741A - Synthesis process of antitumor drug melphalan - Google Patents
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Abstract
The invention relates to the technical field of anticancer drug synthesis, in particular to a synthesis process of an antitumor drug melphalan, and provides the following scheme aiming at the problems that the current traditional melphalan drug is inconvenient to use clinically and contains propylene glycol, so that a patient can generate serious adverse reaction after using the traditional melphalan drug, wherein the synthesis process comprises the following steps: s1: selecting and processing raw materials, S2, preparing the medicine, S3: purification, S4: the invention aims to prepare the melphalan medicine into liquid and use the liquid by an injection method, so that the melphalan medicine is convenient to use clinically, simultaneously, the raw material does not use propylene glycol, the pain of a patient caused by adverse reaction due to the use of the medicine is reduced, and the anticancer rate of the medicine is improved by adopting new raw material for medicine synthesis.
Description
Technical Field
The invention relates to the technical field of anticancer drug synthesis, in particular to a synthesis process of an antitumor drug melphalan.
Background
At present, the traditional melphalan medicine is inconvenient to use clinically, and contains propylene glycol, so that the problem of serious adverse reaction of a patient after use is caused, and therefore, a synthesis process of the anti-tumor medicine melphalan is provided for solving the problem.
Disclosure of Invention
The invention aims to solve the problems that the existing traditional melphalan medicine is inconvenient to use clinically, and contains propylene glycol, so that serious adverse reaction is caused after a patient uses the medicine, and the like.
In order to achieve the purpose, the invention adopts the following technical scheme:
a synthesis process of an antitumor drug melphalan comprises the following steps:
s1: selecting and processing raw materials: selecting raw materials and auxiliary materials required by the synthetic medicine, and pretreating the auxiliary materials;
s2: preparing a medicament: putting the raw materials into a reaction kettle to react to prepare the melphalan medicine;
s3: and (3) purification: purifying the prepared melphalan medicine to prepare a high-purity melphalan medicine;
s4: and (3) drug detection: carrying out drug detection on the prepared high-purity melphalan drug by a professional, and processing the detection result;
preferably, in S1, aniline and ethylene oxide are selected as raw materials for synthesis, acetic acid, phosphorus oxychloride, dimethylformamide, hippuric acid, zinc powder and a mixed acid solution are selected as auxiliary materials, and the selected auxiliary materials are pretreated, wherein acetic acid is prepared into an acetic acid solution with a mass fraction of 60% during pretreatment, and the mixed acid solution is prepared by mixing glacial acetic acid and hydrochloric acid in a volume ratio of 1: 1;
preferably, in S2, the raw materials are put into a reaction kettle to react to prepare a melphalan drug, wherein during the drug preparation, aniline and ethylene oxide react in an acetic acid solution to obtain dianiline (β -via ethyl), the obtained dianiline, phosphorus oxychloride and dimethylformamide simultaneously undergo Vilsmeier reaction and chlorination reaction at a low temperature to generate melphalan, the generated melphalan and hippuric acid are condensed to prepare melphalan, zinc powder undergoes reductive hydrolysis reaction in a mixed acid solution to prepare the melphalan drug, wherein during the condensation of the melphalan and hippuric acid to prepare the melphalan, the obtained product is a racemate, the levorotatory product needs to be obtained by splitting, and the low temperature conditions of the Vilsmeier reaction and the chlorination reaction are that the temperature is controlled to be 0-8 ℃, the reaction time is 30-50min per 100g of raw materials;
preferably, in S3, the prepared melphalan drug is purified to obtain a high-purity melphalan drug, wherein the purification method adopts an evaporation concentration method, the distillation temperature is 100-120 ℃, and the liquid flow rate of the distillation flask is manually calculated during distillation, wherein a uniform meter algorithm is adopted during calculation, the uniform meter algorithm records the increase of the solution in the distillation flask once every 1min, calculates the inflow rate of the solution per second within 1min by using the solution increase, judges and processes the solution according to manual passing rate data, judges that the distillation is not finished if the rate data is greater than 0.2ml/S, judges that the distillation is finished if the rate data is not greater than 0.2ml/S, judges that the distillation is finished if the distillation is not finished, continues to perform distillation if the distillation is finished, stops the distillation for cooling concentration if the distillation is judged to be finished, when cooling concentration is carried out, a temperature detector is used for monitoring the temperature 1cm away from the upper surface of the solution in real time, ice blocks are placed at the bottom of a container filled with the solution, temperature data are judged manually through the temperature detector and are processed through judgment, wherein if the temperature data are higher than 5 ℃, the cooling is judged to be not finished, if the temperature data are not higher than 5 ℃, the cooling is judged to be finished, if the cooling is not finished, cooling concentration is continued, if the cooling is finished, the cooling is stopped, and after the cooling is stopped, the total time of the whole distillation and cooling concentration process is manually recorded as the time required for purification;
preferably, in S4, a professional performs drug detection on the prepared high-purity melphalan drug, wherein the detection content includes drug purity, drug components and whether mutation occurs in the components, the drug purity is lower than 60%, secondary purification is required if the drug purity is not lower than 60%, secondary purification is not performed if mutation occurs in the drug components, the drug prepared in the same time and batch is immediately reported when mutation occurs in the drug components is detected, the steps and the environmental conditions of the synthesis process are checked, the cause of mutation is analyzed, the melphalan drug with the purity of not lower than 60% and the drug components which do not undergo mutation is selected for anti-cancer effect detection after the detection is completed, and when the detection is performed, the injection method is adopted to inject the drug into an experimental object, and the number of cancer cells before and after the injection of the drug is compared, and (5) calculating the anticancer rate.
Compared with the prior art, the invention has the beneficial effects that:
1. the melphalan medicine is prepared into liquid and is used by adopting an injection method, so that the clinical use is convenient.
2. The raw materials do not use propylene glycol, so that the pain of patients caused by adverse reactions due to the use of medicaments is reduced, and the anticancer rate of the medicaments is improved by adopting new raw materials for medicament synthesis.
The invention aims to prepare the melphalan medicine into liquid and use the liquid by adopting an injection method, thereby facilitating clinical use, simultaneously, the raw material does not use propylene glycol, reducing the pain of patients caused by adverse reactions caused by using the medicine, and the new raw material is adopted for medicine synthesis, thereby improving the anticancer rate of the medicine.
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FIG. 1 is a flow chart of a synthesis process of melphalan, an antitumor drug, provided by the invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be described clearly and completely below, and it should be apparent that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments.
Example one
Referring to fig. 1, the synthesis process of the antitumor drug melphalan comprises the following steps:
s1: selecting and processing raw materials: selecting aniline and ethylene oxide as synthetic raw materials, selecting acetic acid, phosphorus oxychloride, dimethylformamide, hippuric acid, zinc powder and a mixed acid solution as auxiliary materials, and simultaneously carrying out pretreatment on the selected auxiliary materials, wherein the acetic acid is prepared into an acetic acid solution with the mass fraction of 60% during pretreatment, and the mixed acid solution is prepared by mixing glacial acetic acid and hydrochloric acid in a volume ratio of 1: 1;
s2: preparing a medicament: the raw materials are put into a reaction kettle to react to prepare the melphalan medicine, aniline and ethylene oxide react in acetic acid solution to obtain dianiline (beta-transethyl) during the preparation of the medicine, and the obtained dianiline, phosphorus oxychloride and dimethylformamide are subjected to Vilsmeier reaction and chlorination reaction at low temperature to generate benzaldehyde nitrogen mustard, the generated benzaldehyde nitrogen mustard and hippuric acid are condensed to prepare benzaldehyde nitrogen mustard azolidone, and zinc powder is subjected to reduction hydrolysis reaction in mixed acid solution to prepare the melphalan medicament, wherein in the process of preparing the benzaldehyde nitrogen mustard azolidone by condensing the benzaldehyde nitrogen mustard and the hippuric acid, the obtained product is raceme and needs to be split to obtain levorotatory substance, the low-temperature conditions of the Vilsmeier reaction and the chlorination reaction are that the temperature is controlled to be 0-8 ℃, and the reaction time is 30-50min for every 100g of raw materials;
s3: and (3) purification: purifying the prepared melphalan medicine to prepare the high-purity melphalan medicine, wherein the purification method adopts an evaporation concentration method, the distillation temperature is 100-120 ℃, the liquid flow rate of a distillation bottle is manually calculated during distillation, a uniform meter algorithm is adopted during calculation, the uniform meter algorithm records the increase of the solution in the distillation bottle once every 1min and calculates the solution inflow rate per second within 1min by using the solution increase, manual passing rate data is used for judging and processing, if the rate data is more than 0.2ml/s, the distillation is not finished, if the rate data is not more than 0.2ml/s, the distillation is finished, if the distillation is not finished, the distillation is continued, if the distillation is finished, the distillation is stopped for cooling concentration, and if the cooling concentration is carried out, a temperature detector is used for monitoring the temperature 1cm away from the upper surface of the solution in real time, placing ice blocks at the bottom of a container filled with the solution, manually judging temperature data through a temperature detector, and processing the ice blocks through judgment, wherein if the temperature data is higher than 5 ℃, the cooling is not finished, if the temperature data is not higher than 5 ℃, the cooling is finished, if the cooling is not finished, the cooling concentration is continuously carried out, if the cooling is finished, the cooling is stopped, and after the cooling is stopped, manually recording the total time of the whole distillation and cooling concentration process as the time required by purification;
s4: and (3) drug detection: the prepared high-purity melphalan medicine is subjected to medicine detection by professionals, wherein the detection content comprises medicine purity, medicine components and whether the components are mutated or not, the medicine purity is lower than 60 percent and needs to be subjected to secondary purification, and the medicine purity is not lower than 60 percent and is not subjected to secondary purification, and the detection of the mutation of the medicine components requires immediate reporting, and the medicine prepared in the same time and batch is destroyed in medical treatment, simultaneously checking the steps and the environmental condition of the synthesis process, analyzing the cause of mutation, selecting melphalan medicine with the purity not lower than 60 percent and the unmutated medicine components after the detection is finished to detect the anti-cancer effect, when the detection is carried out, the injection method is adopted to inject the medicine into the experimental object, and the number of cancer cells before and after the medicine injection is compared to calculate the anticancer rate.
Example two
Referring to fig. 1, the synthesis process of the antitumor drug melphalan comprises the following steps:
s1: selecting and processing raw materials: selecting aniline and ethylene oxide as raw materials for synthesis, and selecting acetic acid, phosphorus oxychloride, dimethylformamide, hippuric acid, zinc powder and mixed acid solution as auxiliary materials;
s2: preparing a medicament: the raw materials are put into a reaction kettle to react to prepare the melphalan medicine, aniline and ethylene oxide react in acetic acid solution to obtain dianiline (beta-transethyl) during the preparation of the medicine, and the obtained dianiline, phosphorus oxychloride and dimethylformamide are subjected to Vilsmeier reaction and chlorination reaction at low temperature to generate benzaldehyde nitrogen mustard, the generated benzaldehyde nitrogen mustard and hippuric acid are condensed to prepare benzaldehyde nitrogen mustard azolidone, and zinc powder is subjected to reduction hydrolysis reaction in mixed acid solution to prepare the melphalan medicament, wherein in the process of preparing the benzaldehyde nitrogen mustard azolidone by condensing the benzaldehyde nitrogen mustard and the hippuric acid, the obtained product is raceme and needs to be split to obtain levorotatory substance, the low-temperature conditions of the Vilsmeier reaction and the chlorination reaction are that the temperature is controlled to be 0-8 ℃, and the reaction time is 30-50min for every 100g of raw materials;
s3: and (3) purification: purifying the prepared melphalan medicine to prepare the high-purity melphalan medicine, wherein the purification method adopts an evaporation concentration method, the distillation temperature is 100-120 ℃, and the liquid flow rate of a distillation bottle is manually calculated during distillation, wherein a uniform metering algorithm is adopted during calculation, the uniform metering algorithm is used for recording the increase of the solution in the distillation bottle once every 1min and calculating the solution inflow rate per second within 1min by using the solution increase, the manual passing rate data is used for judging and processing, if the rate data is more than 0.2ml/s, the distillation is not finished, if the rate data is not more than 0.2ml/s, the distillation is finished, if the distillation is not finished, the distillation is continuously carried out, if the distillation is finished, the distillation is stopped for cooling concentration, and a temperature detector is used for monitoring the temperature 1cm away from the upper surface of the solution in real time during cooling concentration, placing ice blocks at the bottom of a container filled with the solution, manually judging temperature data through a temperature detector, and processing the ice blocks through judgment, wherein if the temperature data is higher than 5 ℃, the cooling is not finished, if the temperature data is not higher than 5 ℃, the cooling is finished, if the cooling is not finished, the cooling concentration is continuously carried out, if the cooling is finished, the cooling is stopped, and after the cooling is stopped, manually recording the total time of the whole distillation and cooling concentration process as the time required by purification;
s4: and (3) drug detection: the prepared high-purity melphalan medicine is subjected to medicine detection by professionals, wherein the detection content comprises medicine purity, medicine components and whether the components are mutated or not, the medicine purity is lower than 60 percent and needs to be subjected to secondary purification, and the medicine purity is not lower than 60 percent and is not subjected to secondary purification, and the detection of the mutation of the medicine components requires immediate reporting, and the medicine prepared in the same time and batch is destroyed in medical treatment, simultaneously checking the steps and the environmental condition of the synthesis process, analyzing the cause of mutation, selecting melphalan medicine with the purity not lower than 60 percent and the unmutated medicine components after the detection is finished to detect the anti-cancer effect, when the detection is carried out, the injection method is adopted to inject the medicine into the experimental object, and the number of cancer cells before and after the medicine injection is compared to calculate the anticancer rate.
EXAMPLE III
Referring to fig. 1, the synthesis process of the antitumor drug melphalan comprises the following steps:
s1: selecting and processing raw materials: selecting aniline and ethylene oxide as synthetic raw materials, selecting acetic acid, phosphorus oxychloride, dimethylformamide, hippuric acid, zinc powder and a mixed acid solution as auxiliary materials, and simultaneously carrying out pretreatment on the selected auxiliary materials, wherein the acetic acid is prepared into an acetic acid solution with the mass fraction of 60% during pretreatment, and the mixed acid solution is prepared by mixing glacial acetic acid and hydrochloric acid in a volume ratio of 1: 1;
s2: preparing a medicament: putting raw materials into a reaction kettle for reaction to prepare a melphalan drug, wherein when the drug is prepared, aniline and ethylene oxide react in an acetic acid solution to obtain dianiline (beta-ethyl), Vilsmeier reaction and chlorination reaction are simultaneously carried out on the obtained dianiline, phosphorus oxychloride and dimethylformamide at low temperature to generate benzaldehyde nitrogen mustard, then the generated benzaldehyde nitrogen mustard is condensed with hippuric acid to prepare benzaldehyde nitrogen mustard ketole, and zinc powder is subjected to reduction hydrolysis reaction in a mixed acid solution to prepare the melphalan drug;
s3: and (3) purification: purifying the prepared melphalan medicine to prepare the high-purity melphalan medicine, wherein the purification method adopts an evaporation concentration method, the distillation temperature is 100-120 ℃, and the liquid flow rate of a distillation bottle is manually calculated during distillation, wherein a uniform metering algorithm is adopted during calculation, the uniform metering algorithm is used for recording the increase of the solution in the distillation bottle once every 1min and calculating the solution inflow rate per second within 1min by using the solution increase, the manual passing rate data is used for judging and processing, if the rate data is more than 0.2ml/s, the distillation is not finished, if the rate data is not more than 0.2ml/s, the distillation is finished, if the distillation is not finished, the distillation is continuously carried out, if the distillation is finished, the distillation is stopped for cooling concentration, and a temperature detector is used for monitoring the temperature 1cm away from the upper surface of the solution in real time during cooling concentration, placing ice blocks at the bottom of a container filled with the solution, manually judging temperature data through a temperature detector, and processing the ice blocks through judgment, wherein if the temperature data is higher than 5 ℃, the ice blocks are judged to be not finished, if the temperature data is not higher than 5 ℃, the ice blocks are judged to be finished, the ice blocks are judged to be continuously cooled and concentrated, if the ice blocks are judged to be finished, the ice blocks are stopped, and after the ice blocks are stopped, manually recording the total time of the whole distillation and cooling and concentrating process as the time required by purification;
s4: and (3) drug detection: the prepared high-purity melphalan medicine is subjected to medicine detection by professionals, wherein the detection content comprises medicine purity, medicine components and whether the components are mutated or not, the medicine purity is lower than 60 percent and needs to be subjected to secondary purification, and the medicine purity is not lower than 60 percent and is not subjected to secondary purification, and the detection of the mutation of the medicine components requires immediate reporting, and the medicine prepared in the same time and batch is destroyed in medical treatment, simultaneously checking the steps and the environmental condition of the synthesis process, analyzing the cause of mutation, selecting melphalan medicine with the purity not lower than 60 percent and the unmutated medicine components after the detection is finished to detect the anti-cancer effect, when the detection is carried out, the injection method is adopted to inject the medicine into the experimental object, and the number of cancer cells before and after the medicine injection is compared to calculate the anticancer rate.
Example four
Referring to fig. 1, the synthesis process of the antitumor drug melphalan comprises the following steps:
s1: selecting and processing raw materials: selecting aniline and ethylene oxide as synthetic raw materials, selecting acetic acid, phosphorus oxychloride, dimethylformamide, hippuric acid, zinc powder and a mixed acid solution as auxiliary materials, and simultaneously carrying out pretreatment on the selected auxiliary materials, wherein the acetic acid is prepared into an acetic acid solution with the mass fraction of 60% during pretreatment, and the mixed acid solution is prepared by mixing glacial acetic acid and hydrochloric acid in a volume ratio of 1: 1;
s2: preparing a medicament: the raw materials are put into a reaction kettle to react to prepare the melphalan medicine, aniline and ethylene oxide react in acetic acid solution to obtain dianiline (beta-transethyl) during the preparation of the medicine, and the obtained dianiline, phosphorus oxychloride and dimethylformamide are subjected to Vilsmeier reaction and chlorination reaction at low temperature to generate benzaldehyde nitrogen mustard, the generated benzaldehyde nitrogen mustard and hippuric acid are condensed to prepare benzaldehyde nitrogen mustard azolidone, and zinc powder is subjected to reduction hydrolysis reaction in mixed acid solution to prepare the melphalan medicament, wherein in the process of preparing the benzaldehyde nitrogen mustard azolidone by condensing the benzaldehyde nitrogen mustard and the hippuric acid, the obtained product is raceme and needs to be split to obtain levorotatory substance, the low-temperature conditions of the Vilsmeier reaction and the chlorination reaction are that the temperature is controlled to be 0-8 ℃, and the reaction time is 30-50min for every 100g of raw materials;
s3: and (3) purification: purifying the prepared melphalan medicine to prepare the high-purity melphalan medicine, wherein the purification method adopts an evaporation concentration method, the distillation temperature is 100-120 ℃, the liquid flow rate of a distillation bottle is manually calculated during distillation, a uniform meter algorithm is adopted during calculation, the uniform meter algorithm records the increase of the solution in the distillation bottle once every 1min and calculates the solution inflow rate per second within 1min by using the solution increase, manual passing rate data is used for judging and processing, if the rate data is more than 0.2ml/s, the distillation is not finished, if the rate data is not more than 0.2ml/s, the distillation is finished, if the distillation is not finished, the distillation is continued, if the distillation is finished, the distillation is stopped for cooling concentration, and if the cooling concentration is carried out, a temperature detector is used for monitoring the temperature 1cm away from the upper surface of the solution in real time, placing ice blocks at the bottom of the container filled with the solution;
s4: and (3) drug detection: the prepared high-purity melphalan medicine is subjected to medicine detection by professionals, wherein the detection content comprises medicine purity, medicine components and whether the components are mutated or not, the medicine purity is lower than 60 percent and needs to be subjected to secondary purification, and the medicine purity is not lower than 60 percent and is not subjected to secondary purification, and the detection of the mutation of the medicine components requires immediate reporting, and the medicine prepared in the same time and batch is destroyed in medical treatment, simultaneously checking the steps and the environmental condition of the synthesis process, analyzing the cause of mutation, selecting melphalan medicine with the purity not lower than 60 percent and the unmutated medicine components after the detection is finished to detect the anti-cancer effect, when the detection is carried out, the injection method is adopted to inject the medicine into the experimental object, and the number of cancer cells before and after the medicine injection is compared to calculate the anticancer rate.
EXAMPLE five
Referring to fig. 1, the synthesis process of the antitumor drug melphalan comprises the following steps:
s1: selecting and processing raw materials: selecting aniline and ethylene oxide as synthetic raw materials, selecting acetic acid, phosphorus oxychloride, dimethylformamide, hippuric acid, zinc powder and a mixed acid solution as auxiliary materials, and simultaneously carrying out pretreatment on the selected auxiliary materials, wherein the acetic acid is prepared into an acetic acid solution with the mass fraction of 60% during pretreatment, and the mixed acid solution is prepared by mixing glacial acetic acid and hydrochloric acid in a volume ratio of 1: 1;
s2: preparing a medicament: the raw materials are put into a reaction kettle to react to prepare the melphalan medicine, wherein aniline and ethylene oxide react in acetic acid solution to obtain dianiline (beta-transethyl) during the medicine preparation, and the obtained dianiline, phosphorus oxychloride and dimethylformamide are subjected to Vilsmeier reaction and chlorination reaction at low temperature to generate benzaldehyde nitrogen mustard, the generated benzaldehyde nitrogen mustard and hippuric acid are condensed to prepare benzaldehyde nitrogen mustard azolidone, and zinc powder is subjected to reduction hydrolysis reaction in mixed acid solution to prepare the melphalan medicament, wherein in the process of preparing the benzaldehyde nitrogen mustard azolidone by condensing the benzaldehyde nitrogen mustard and the hippuric acid, the obtained product is raceme and needs to be split to obtain levorotatory substance, the low-temperature conditions of the Vilsmeier reaction and the chlorination reaction are that the temperature is controlled to be 0-8 ℃, and the reaction time is 30-50min for every 100g of raw materials;
s3: and (3) purification: purifying the prepared melphalan medicine to prepare the high-purity melphalan medicine, wherein the purification method adopts an evaporation concentration method, the distillation temperature is 100-120 ℃, the liquid flow rate of a distillation bottle is manually calculated during distillation, a uniform meter algorithm is adopted during calculation, the uniform meter algorithm records the increase of the solution in the distillation bottle once every 1min and calculates the solution inflow rate per second within 1min by using the solution increase, manual passing rate data is used for judging and processing, if the rate data is more than 0.2ml/s, the distillation is not finished, if the rate data is not more than 0.2ml/s, the distillation is finished, if the distillation is not finished, the distillation is continued, if the distillation is finished, the distillation is stopped for cooling concentration, and if the cooling concentration is carried out, a temperature detector is used for monitoring the temperature 1cm away from the upper surface of the solution in real time, and placing ice blocks at the bottom of a container filled with the solution, manually judging temperature data through a temperature detector, and processing the ice blocks through judgment, wherein if the temperature data is higher than 5 ℃, the cooling is not finished, if the temperature data is not higher than 5 ℃, the cooling is finished, if the cooling is not finished, the cooling concentration is continuously carried out, if the cooling is finished, the cooling is stopped, and after the cooling is stopped, manually recording the total time of the whole distillation and cooling concentration process as the time required by purification.
The synthesis process of melphalan, which is one of the antitumor drugs in the first example, the second example, the third example, the fourth example and the fifth example, is tested, and the following results are obtained:
the synthesis process of the antitumor drugs melphalan prepared in the first embodiment, the second embodiment, the third embodiment, the fourth embodiment and the fifth embodiment has the advantage that the anticancer rate is remarkably improved compared with the anticancer rate of the existing process, and the first embodiment is the best embodiment.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and equivalent alternatives or modifications according to the technical solution and the inventive concept of the present invention should be covered by the scope of the present invention.
Claims (8)
1. A synthesis process of an antitumor drug melphalan is characterized by comprising the following steps:
s1: selecting and processing raw materials: selecting raw materials and auxiliary materials required by the synthetic medicine, and pretreating the auxiliary materials;
s2: preparing a medicament: putting the raw materials into a reaction kettle to react to prepare the melphalan medicine;
s3: and (3) purification: purifying the prepared melphalan medicine to prepare the high-purity melphalan medicine;
s4: and (3) drug detection: the prepared high-purity melphalan medicine is subjected to medicine detection by a professional, and the detection result is processed.
2. The process for synthesizing melphalan as an antitumor drug according to claim 1, wherein in S1, aniline and ethylene oxide are selected as raw materials for synthesis, and acetic acid, phosphorus oxychloride, dimethylformamide, hippuric acid, zinc powder and a mixed acid solution are selected as auxiliary materials.
3. The process for synthesizing melphalan as an antitumor drug according to claim 2, characterized in that selected auxiliary materials are pretreated, wherein acetic acid is prepared into an acetic acid solution with the mass fraction of 60% during pretreatment, and a mixed acid solution is prepared at the same time, wherein the mixed acid solution is prepared by mixing glacial acetic acid and hydrochloric acid in a volume ratio of 1: 1.
4. The process of claim 1, wherein in step S2, the raw materials are charged into a reactor to react to prepare the melphalan drug, wherein the drug is prepared by reacting aniline and ethylene oxide in an acetic acid solution to obtain dianiline, performing Vilsmeier reaction and chlorination reaction on the obtained dianiline, phosphorus oxychloride and dimethylformamide at low temperature to generate benzaldehyde nitrogen mustard, condensing the generated benzaldehyde nitrogen mustard and hippuric acid to obtain benzaldehyde nitrogen mustard azolone, and performing reductive hydrolysis reaction on the benzaldehyde nitrogen mustard and zinc powder in a mixed acid solution to obtain the melphalan drug.
5. The process for synthesizing melphalan, an antitumor drug, according to claim 4, wherein during the condensation of benzaldehyde nitrogen mustard and hippuric acid to obtain benzaldehyde nitrogen mustard oxazolone, the obtained product is racemic body, which needs to be resolved to obtain levorotatory body, and the Vilsmeier reaction and the chlorination reaction are carried out at low temperature of 0-8 ℃ for 30-50min per 100g of raw material.
6. The process of claim 4, wherein in S3, the prepared melphalan is purified to obtain high-purity melphalan, wherein the purification method adopts an evaporation concentration method, the distillation temperature is 100-, and stopping distillation and cooling concentration when the distillation is judged to be finished.
7. The process according to claim 6, wherein the temperature of 1cm above the upper surface of the solution is monitored in real time by a temperature detector during the cooling concentration, ice cubes are placed at the bottom of the container containing the solution, the temperature data is manually judged by the temperature detector and processed by the judgment, wherein the temperature data is higher than 5 ℃ to judge that the cooling is not completed, the temperature data is not higher than 5 ℃ to judge that the cooling is completed, the cooling concentration is continued if the cooling is not completed, the cooling is stopped if the cooling is completed, and the total time of the whole distillation and cooling concentration process is manually recorded as the time required for purification after the cooling is stopped.
8. The process according to claim 1, wherein in step S4, the prepared high-purity melphalan is tested by professional personnel, wherein the test contents include drug purity, drug components and whether mutation occurs in the components, the test results are used for processing, secondary purification is required when the drug purity is lower than 60%, secondary purification is not required when the drug purity is not lower than 60%, the drug components are detected to have mutation and are reported immediately, the drugs prepared in the same time and batch are destroyed medically, the steps and environmental conditions of the synthesis process are checked at the same time, the cause of mutation is analyzed, the melphalan with purity of not lower than 60% and no mutation occurs in the drug components is selected for testing the anti-cancer effect, and the injection method is used for injecting the drug into the experimental object during testing, and comparing the number of cancer cells before and after the injection of the medicine to calculate the anticancer rate.
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