Method for synthesizing dovitnib intermediate in microchannel reactor

A technology of microchannel reactor and dovitinib, which is applied in the direction of organic chemistry, can solve the problems of low catalyst recovery times, poor safety, high energy consumption, etc., achieve stable online production and post-processing, reduce production costs, and operate simple effect

Inactive Publication Date: 2018-10-23
HEILONGJIANG XINCHUANG BIOLOGICAL TECH DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] In order to solve the problems of poor safety, high energy consumption, easy oxidation, low yield, high cost, and low times of catalyst recovery and application in the process of synthesizing dovitinib intermediates in traditional high-pressure catalytic hydrogenation reactors, the present invention provides a A method for synthesizing dovitinib intermediates in a microchannel reactor, the chemical reaction formula is as follows:

Method used

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  • Method for synthesizing dovitnib intermediate in microchannel reactor
  • Method for synthesizing dovitnib intermediate in microchannel reactor
  • Method for synthesizing dovitnib intermediate in microchannel reactor

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Embodiment 1

[0046] This embodiment provides a method for synthesizing dovitinib intermediates in a microchannel reactor, and the specific steps are as follows:

[0047] 1) Weigh 200g of 5-(4-methylpiperazine)-2-nitroaniline, then add it to 4L of anhydrous methanol, then add 5g of Pd / C catalyst with a mass content of 10%, stir well Mix to form material I, transport material I to the preheating module 1 of the microchannel reactor for preheating, and enter the reaction module group of the microchannel reactor after preheating;

[0048] 2) Hydrogen is delivered to the reaction module group of the microchannel reactor and step 1) reacts with the preheated material I in the reaction module group, wherein: adjust the flow rate of the slurry pump to make the flow rate of the material I 30.0g / min , adjust H 2 The flow rate of the gas flowmeter is 500ml / min, the molar ratio of 5-(4-methylpiperazine)-2-nitroaniline to hydrogen is 1:3.0, the reaction temperature is 90°C, and the temperature of the ...

Embodiment 2

[0050] This embodiment provides a method for synthesizing dovitinib intermediates in a microchannel reactor, and the specific steps are as follows:

[0051] 1) Weigh 200g of 5-(4-methylpiperazine)-2-nitroaniline, then add it to 4L of dehydrated ethanol, then add 10g of Pd / C catalyst with a mass content of 5%, stir well Mix to form material I, transport material I to the preheating module 1 of the microchannel reactor for preheating, and enter the reaction module group of the microchannel reactor after preheating;

[0052] 2) Hydrogen is delivered to the reaction module group of the microchannel reactor and step 1) the material I after preheating is reacted in the reaction module group, wherein: adjust the flow rate of the slurry pump so that the flow rate of the material I is 35.0g / min , adjust H 2 The flow rate of the gas flowmeter is 600ml / min, the molar ratio of 5-(4-methylpiperazine)-2-nitroaniline to hydrogen is 1:3.1, the reaction temperature is 80°C, and the temperatur...

Embodiment 3

[0054] This embodiment provides a method for synthesizing dovitinib intermediates in a microchannel reactor, and the specific steps are as follows:

[0055] 1) Weigh 300g of 5-(4-methylpiperazine)-2-nitroaniline, then add it to 5L of dehydrated ethanol, then add 12g of Pt mass content as a Pt / C catalyst with a mass content of 10%, fully stir Mix to form material I, transport material I to the preheating module 1 of the microchannel reactor for preheating, and enter the reaction module group of the microchannel reactor after preheating;

[0056] 2) Hydrogen is delivered to the reaction module group of the microchannel reactor and step 1) the material I after preheating is reacted in the reaction module group, wherein: adjust the flow rate of the slurry pump so that the flow rate of the material I is 25.0g / min , adjust H 2 The flow rate of the gas flowmeter is 580ml / min, the molar ratio of 5-(4-methylpiperazine)-2-nitroaniline to hydrogen is 1:3.5, the reaction temperature is 1...

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Abstract

The invention discloses a method for synthesizing a dovitnib intermediate in a microchannel reactor and belongs to the technical field of antitumor drug synthesis in organic synthesis. The method comprises adding 5-(4-methylpiperazine)-2-nitroaniline into an organic solvent, adding an activated carbon-loaded precious metal catalyst into the solution to obtain a mixture as a material I, conveying the material I into a preheating module of the microchannel reactor, carrying out preheating, feeding the preheated material into a reaction module set, feeding hydrogen into the reaction module set ofthe microchannel reactor so that the hydrogen and the preheated material I undergo a reaction in the reaction module set, collecting the reaction liquid flowing out of a cooling module and carrying out post-treatment to obtain the dovitnib intermediate 4-(4-methylpiperazinyl)-1, 2-phenylenediamine. The method can effectively shorten the reaction time, greatly reduce the combustion and explosion safety hazard caused by hydrogen leakage, and is suitable for the process of synthesizing the dovitnib intermediate.

Description

technical field [0001] The invention relates to a method for synthesizing a dovitinib intermediate in a microchannel reactor, and belongs to the technical field of synthesizing antitumor drugs in organic synthesis. Background technique [0002] Dovitinib is a new type of anti-tumor drug developed by Chiron Corporation of the United States, which is mainly an oral small molecule inhibitor of TKI protein tyrosine kinase. Its structure is a derivative of benzimidazolone, and its chemical formula is as follows: [0003] [0004] Dovitinib can be directly applied to tumor cells and the blood vessels and stroma that provide nutritional support for the tumor. It has inhibitory effects on many growth factors and can treat blood cancers and solid tumors. Due to its strong anti-tumor and anti-angiogenic activities in different tumor models, it has been used in the treatment of various malignant tumors in the clinical stage, and the market prospect is widely optimistic. [0005] 4...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/135
CPCC07D295/135
Inventor 任吉秋杨昆李海涛
Owner HEILONGJIANG XINCHUANG BIOLOGICAL TECH DEV CO LTD
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