A kind of preparation method of ceritinib intermediate

A technology of ceritinib and intermediates, which is applied in the field of synthesis of organic compounds, can solve the problems of short route and low cost, and achieve the effects of low cost, mild reaction conditions and easy availability of raw materials

Active Publication Date: 2017-02-22
常州市勇毅生物药业有限公司
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Problems solved by technology

[0006] The purpose of the present invention is: solve the problem of synthetic route of ceritinib in the

Method used

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  • A kind of preparation method of ceritinib intermediate
  • A kind of preparation method of ceritinib intermediate
  • A kind of preparation method of ceritinib intermediate

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Embodiment 1

[0016] Step 1: Add 422mg (6.45mmol) of zinc powder and 4ml of DMAC (dimethylacetamide) into a dry four-necked bottle under the protection of nitrogen gas. 90 microliters (1 mmol) of 1,2-dibromoethane, heated to an internal temperature of 56 degrees, a gray suspension in the reaction bottle, after heating for 5 minutes, cooling the reaction solution to about 33 degrees, TMSCl (trimethyl Chlorosilane (170 microliters, 1.34mmol) was added, exothermic, the temperature naturally rose to 57 degrees, the reaction solution was cooled to 40 degrees, and kept for 15min, SR-1 (1.02g, 3.26mmol), DMAC0.5ml mixed solution Add dropwise, exothermic reaction, the reaction solution is cooled to room temperature, stirred for 1H, after the reaction is complete, suction filtration is used under nitrogen protection and directly used in the next step reaction (to be used within 1HR, the concentration of the solution is titrated for iodine content).

[0017] The second step: In a 500ml four-neck flas...

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Abstract

The invention relates to a preparation method of ceritinib. The preparation method comprises the following steps: (1) reacting metal powder with N-t-butyloxycarboryl-4 iodine piperidine with a structural formula of SR-1 to generate a metal coupling agent with a structural formula of SR-2; (2) performing a coupling reaction on the metal coupling agent SR-2 and 1-bromo-5-isopropoxy-2-methyl-4-nitrobenzene to generate a compound SR-3; (3) performing hydrogenation reduction on the compound SR-3, and removing BOC amino protection to generate the ceritinib SR-4. According to the invention, a novel preparation method of the ceritinib is developed. The synthetic route is very short; the yield is high; raw materials can be easily obtained and are low in cost; reaction conditions are very mild and easy to control; therefore, the preparation method is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a method for synthesizing organic compounds, in particular to a method for preparing an intermediate of ceritinib. Background technique [0002] Ceritinib is an anticancer drug approved by the FDA on April 29, 2014. Ceritinib is an ALK inhibitor (Anaplastic Lymphoma Kinase), indicated for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed after crizotinib treatment or who are intolerant to crizotinib. The trade name is Zykadia, developed by Novartis Pharmaceuticals. [0003] The synthesis of ceritinib uses the convergence method, first synthesizing two fragments with similar molecular weights, and then splicing the two fragments (JMC, 2013, 5675). The first fragment starts from compound 1, after nitration by SNAr reaction with isopropanol to give 2, 2 and 3 PtO after Suzuki coupling 2 Fragment 4 was obtained by catalytic hydrogenation to...

Claims

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Application Information

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IPC IPC(8): C07D211/26C07D401/12
CPCY02P20/55
Inventor 潘勇夏晓丽李玉涛崔伟杰
Owner 常州市勇毅生物药业有限公司
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