Method for full-automatically synthesizing <18>F-marked pyrimidine acrylamide based EGFR positive-electron tracer agent through one-step method

Abstract

The invention discloses a method for full-automatically synthesizing a <18>F-marked pyrimidine acrylamide based EGFR positive-electron tracer agent through a one-step method, and belongs to the fieldof chemical synthesis. The method sequentially comprises the following steps that (1) <18>F ions from an accelerator and water are conveyed to a receiving bottle and guided into an anion exchange column; (2) <18>F ions in the anion exchange column are eluted with a mixed solution formed by strong alkali and weak acid salt, acetonitrile and ionic liquid, and then are conveyed to a reaction bottle;(3) precursor is dissolved in a DMSO or acetonitrile or DMF solution, a buffer solution is added into the former solution to enable pH of the former solution to be 2, and the obtained solution is added into the reaction bottle and heated under protection of inert gas; (4) the temperature is lowered, and coarse products in the reaction bottle are purified through a solid-phase extraction C18 pillaret; and (5) target products of a solution obtained in the step (4) are separated and collected, so that the positive-electron tracer agent is obtained. The method has the characteristics of multi-purpose, large yield, high efficiency, short synthesis time, low cost and the like, and can meet the requirement for large-scale production.

Description

technical field [0001] The invention relates to a compound synthesized by fluorination substitution reaction 18 F-labeled pyrimidine acrylamide EGFR positron tracer and preparation method thereof, the invention belongs to the field of chemical synthesis, Background technique [0002] Epidermal growth factor receptor (EGFR, ErbB) is a cell surface receptor of the extracellular protein ligand of class I epidermal growth factor family. It has tyrosine kinase activity and is an important transmembrane receptor. The high expression of EGFR can promote the proliferation, angiogenesis, adhesion, invasion and metastasis of tumor cells, so EGFR tyrosine kinase inhibitors have become a hot spot in the research of anti-tumor drugs. Studies have shown that the mutation at the T790M site of the EGFR gene is the main cause of drug resistance. In order to overcome the drug resistance of existing drugs, this paper uses the EGFR inhibitor AZD-9291 as a lead compound for structural modificat...

AI Technical Summary

Problems solved by technology

[0012] (2) The current methods and limitations of detecting whether EGFR is mutated, screening the beneficiaries of small molecule EGFR inhibitors, and monitoring the efficacy of treatment

[0014] After conventional DNA sequencing and PCR technique to amplify the EGFR gene, although DNA analysis, fluorescent RT-PCR, and high performance liquid chromatography can determine the mutation of the EGFR gene, there are limitations in technical analysis

①Living material collection: It is an in vitro and invasive examination, which increases the risk of lesion metastasis after operation; ②The requirements for tissue collection are high, and are greatly affected by the composition and experimental conditions; , and whether it can represent the relapsed tumor status of patients before receiving TKI treatment needs further study; ④The operation is complex, time-consuming, and random; ⑤The instruments required for detection are expensive and the efficiency is low. Units can provide this gene detection method, so it is difficult to popularize and apply it on a large scale. At present, only about one fifth of patients can find suitable tissue samples for detection; ⑥ In the latest research, some people try to detect EGFR mutations from pleural effusion and serum , but due to the extremely small sample size of EGFR obtained in this way, the detection rate, consistency and accuracy are low; ⑦ traditional imaging techniques also have many uncertain factors in monitoring the efficacy of EGFR targeted therapy Imaging methods can judge the efficacy of EGFR-targeted therapy

However, reversible EGFR-like positron tracers have a short residence time and a relatively low uptake rate in tumor cells

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