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Preparation method of 5-(2-fluorophenyl)-1H-pyrrole-3-formaldehyde

A technology of fluorophenyl and pyrrole, applied in the field of preparation of 5--1H-pyrrole-3-carbaldehyde, can solve problems such as unfavorable industrialized production, long process route, unfavorable industrialization and the like

Pending Publication Date: 2021-11-16
HANGZHOU HUANGSEN BIOLOGICAL TECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The route is also longer, which is not conducive to industrialization
[0010] The existing process route for preparing 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde is relatively long, which is unfavorable for industrialized production

Method used

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  • Preparation method of 5-(2-fluorophenyl)-1H-pyrrole-3-formaldehyde

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preparation example Construction

[0036] The invention provides a kind of preparation method of 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde, comprising the following steps:

[0037] Mix 2-[2-(2-fluorophenyl)-2-oxoethyl]malononitrile, Raney nickel, solvent, acidic pH regulator and reducing agent, and carry out one-step reaction under acidic conditions to obtain 5-(2-Fluorophenyl)-1H-pyrrole-3-carbaldehyde.

[0038] In the present invention, the 2-[2-(2-fluorophenyl)-2-oxoethyl]malononitrile is preferably a conventional commercially available product, more preferably purchased from Shandong Xuande Pharmaceutical Technology Co., Ltd._. In the present invention, the mass ratio of the 2-[2-(2-fluorophenyl)-2-oxoethyl]malononitrile and Raney nickel is preferably 1:0.2~0.5, more preferably 1: 0.35-0.49.

[0039] In the present invention, the solvent preferably includes one or more of alcohol, water and tetrahydrofuran, more preferably a mixture of alcohol and water or a mixture of tetrahydrofuran and water. In th...

Embodiment 1

[0073] 36.5g of 2-[2-(2-fluorophenyl)-2-oxoethyl]malononitrile purchased from Shandong Xuande Pharmaceutical Technology Co., Ltd., 130mL of tetrahydrofuran, 105mL of acetic acid and 50mL of water were stirred at 25°C Mix to obtain the first reaction solution;

[0074] Disperse 18g of Raney nickel in the first reaction solution to obtain a second reaction solution;

[0075] Add 120mL of sodium hypophosphite aqueous solution with a mass concentration of 0.76g / mL to the second reaction solution dropwise at a rate of 12 drops / min, and the addition is completed within 30 minutes; one-step reaction at 40°C for 3 hours;

[0076] Filter the product after the reaction, wash the filter residue twice with 50mL tetrahydrofuran, separate the filtrate obtained by filtration, and distill the upper organic layer at 60°C under reduced pressure; dissolve the solid obtained by distillation in 200mL ethyl acetate and 200mL molar concentration In the mixed solution of 1mol / L hydrochloric acid aqu...

Embodiment 2

[0079] 20.2g of 2-[2-(2-fluorophenyl)-2-oxoethyl]malononitrile purchased from Shandong Xuande Pharmaceutical Technology Co., Ltd., 80mL of ethanol, 60mL of acetic acid and 30mL of water were stirred at 25°C Mix to obtain the first reaction solution;

[0080] Disperse 10g of Raney nickel in the first reaction solution to obtain a second reaction solution;

[0081] Add 700mL of sodium hypophosphite aqueous solution with a mass concentration of 0.84g / mL to the second reaction solution dropwise at a rate of 13 drops / min, and the addition is completed within 30 minutes; one-step reaction at 38°C for 3 hours;

[0082] Filter the product after the reaction, wash the filter residue twice with 50mL tetrahydrofuran, separate the filtrate obtained by filtration, and distill the upper organic layer at 60°C under reduced pressure; dissolve the solid obtained by distillation in 200mL ethyl acetate and 200mL molar concentration In the mixed solution of hydrochloric acid aqueous solution of ...

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Abstract

The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a preparation method of 5-(2-fluorophenyl)-1H-pyrrole-3-formaldehyde. The preparation method of 5-(2-fluorophenyl)-1H-pyrrole-3-formaldehyde provided by the invention comprises the following steps of: mixing 2-[2-(2-fluorophenyl)-2-oxoethyl] malononitrile, raney nickel, a solvent, an acidic pH value regulator and a reducing agent, and carrying out one-step reaction under an acidic condition to obtain 5-(2-fluorophenyl)-1H-pyrrole-3-formaldehyde. According to the preparation method provided by the invention, 5-(2-fluorophenyl)-1H-pyrrole-3-formaldehyde can be synthesized in one step by taking 2-[2-(2-fluorophenyl)-2-oxoethyl] malononitrile as a main reactant and Raney nickel as a catalyst, the operation is simple, the reaction conditions are mild, and the reaction steps are reduced.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a preparation method of 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde. Background technique [0002] Vonoprazan fumarate (TAK-438, Vonoprazan fumarate), the chemical name is 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3- Base)-N-methylmethylamine fumarate is a new type of oral anti-gastric acid jointly launched by Takeda Pharmaceutical and Otsuka Pharmaceutical, which is used for erosive esophagitis, gastric ulcer, and duodenal ulcer. On December 26, 2014, it was approved for marketing in Japan (trade name Takecab) for the treatment of acid-related diseases. Vonorazan fumarate belongs to potassium ion (K + ) Competitive acid blocker (P-CAB), is a reversible proton pump agent. After this product enters the human body, it passes the K + with H + -K + - The combination of ATPase (proton pump) terminates the secretion of gastric ac...

Claims

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Application Information

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IPC IPC(8): C07D207/333
CPCC07D207/333
Inventor 姚红罗瑾郑杰杨玉平张应军谭艳红
Owner HANGZHOU HUANGSEN BIOLOGICAL TECH CO LTD
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