Synthesis method of EGFR (epidermal growth factor receptor) inhibitor Dacomitinib

Abstract

The invention discloses a synthesis method of an EGFR (epidermal growth factor receptor) inhibitor Dacomitinib. The method comprises ten steps for synthesis reaction and specifically comprises the following steps of: firstly performing cyclization on 2-amino-4-fluorobenzoic acid and formamide at high temperature, then successively performing nitration reaction, hydrogenation reduction, amidation reaction, methoxylation reaction and chlorination reaction; and finally splicing with 3-chloro-4-fluoroaniline to prepare the EGFR inhibitor Dacomitinib. Main starting materials involved in the synthesis method are raw materials which are easy to purchase on the market, and the synthesis method has the advantages of high yield and high molecular economic efficiency, and is a high-efficient, green and environment-friendly process method suitable for industrial mass production.

Description

technical field [0001] The invention relates to the field of pharmaceutical chemical synthesis, in particular to a method for synthesizing EGFR inhibitor Dacomitinib. Background technique [0002] The discovery of mutated epidermal growth factor receptor (EGFR), one of the driving genes of lung cancer, opens the door for targeted therapy in non-small cell lung cancer (NSCLC). In 2002, gefitinib, the first small molecule inhibitor targeting epidermal growth factor receptor (EGFR) tyrosine kinase, was launched on the market. Similar studies emerge in endlessly, and the evidence is also increasing. The range of TKIs recommended by various guidelines covers second-line, third-line treatment, first-line treatment, and even maintenance treatment of advanced NSCLC. EGFR-TKIs not only lead the trend and trend of molecular targeted therapy for lung cancer, but also become an indisputable successful model of individualized therapy for lung cancer. [0003] Dacomitinib is a pan-huma...

AI Technical Summary

Problems solved by technology

[0007] The main disadvantages of this method are that the protection and deprotection of amino groups are difficult, the reaction is incomplete, new impurities are produced, the synthetic route is long, the total yield is low, and the cost is high, which is not conducive to industrial production and promotion.