Method for synthesizing lapatinib intermediate in microchannel reactor

Abstract

The invention provides a method for synthesizing a lapatinib intermediate in a microchannel reactor, and belongs to the field of anticancer drug synthesis in organic synthesis. The method solves the problems that in a traditional synthesis process of a high-temperature high-pressure catalytic hydrogenation reactor, the yield and purity are low, violent explosion easily occurs to generate dangers,dechlorination and ether oxygen bond rupture and degradation are caused when the reaction time under high temperature is long, and the recycling and reusing rate of a catalyst is low. The method for synthesizing the lapatinib intermediate in the microchannel reactor comprises the following steps that 1) 2-chloro-1-(3-fluorobenzyloxy)-4-nitrobenzene is added into an organic solvent, and the activated-carbon-loaded noble metal catalyst is added, serves as a first material and enters a preheating module of the microchannel reactor or a microreactor; 2) the preheated first material and a second material hydrogen are injected into a reaction module set of the microchannel reactor or the microreactor for a reaction respectively, a reaction solution flowing out of a cooling module is collected, and 3-chloro-4-(3-fluorobenzyloxy)aniline is obtained after post-treatment. The method is suitable for the synthesis of the lapatinib intermediate.

Description

technical field [0001] The invention belongs to the field of synthesis of anticancer drugs in organic synthesis, and in particular relates to a synthesis method of a lapatinib intermediate. Background technique [0002] Lapatinib is an anticancer drug developed by GlaxoSmithKline. Its chemical name is N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5 -[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine, approved by the U.S. FDA in March 2007, for use in combination with capecitabine for the treatment of Advanced or metastatic breast cancer with overexpression of human epidermal growth factor receptor 2 (HER2) and previous treatment including anthracyclines, paclitaxel, and trastuzumab. In combination with letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer overexpressing the HER2 receptor. In recent years, there have been more and more studies on lapatinib in other tumor treatment fields. [0003] Among...

AI Technical Summary

Problems solved by technology

[0006] In order to solve the problem of low yield, poor purity, danger of violent explosion, long reaction time at high temperature, resulting in ether oxygen bond breakage, dechlorination degradation, low efficiency of catalyst recovery and application in the traditional high-pressure catalytic hydrogenation reactor synthesis process, environmental protection Problems such as serious pollution, the invention provides a kind of method for the synthetic lapatinib intermediate of microchannel reactor, chemical reaction formula is as follows:

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