Check patentability & draft patents in minutes with Patsnap Eureka AI!

Vonoprazan intermediate as well as preparation method and application thereof

An intermediate and reaction technology, applied in the field of medicinal chemistry, can solve the problems of residual toxic impurities and cumbersome operation process, and achieve the effects of high reaction efficiency, avoiding hydrogenation reaction, and high yield

Pending Publication Date: 2022-03-08
LUNAN PHARMA GROUP CORPORATION
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] In view of the cumbersome operation process and residual toxic impurities in the current preparation process of vonoprazan, the present invention aims to provide a method that can simplify the synthesis steps of vonoprazan, change the synthesis thinking of introducing nitrogen methyl and reduce toxic impurities. The preparation method of the residual intermediate compound N-methyl-1-(3-pyridylsulfonyl)-2-bromo-1H-pyrrole-3-methylamine; the present invention also provides a relatively simple operation and efficient reaction A technical method suitable for industrialized production of Vonorazan that responds to environmental protection

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Vonoprazan intermediate as well as preparation method and application thereof
  • Vonoprazan intermediate as well as preparation method and application thereof
  • Vonoprazan intermediate as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] Preparation of Example 1 Compound 5

[0074] Dissolve 31.2g of 1-(3-pyridylsulfonyl)-2-bromo-1H-pyrrole-3-carbonitrile in 320mL of ethanol aqueous solution (80%), add 5.4mL of concentrated sulfuric acid solution, heat up to 45°C, and keep the reaction for 8h After the reaction, 500 mL of purified water was added, extracted three times with 500 mL of ethyl acetate, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was dried under reduced pressure to obtain an oily compound 3, namely 1-(3-pyridylsulfonyl)- 2-Bromo-1H-pyrrole-3-carboxylic acid, 90.1% yield, ESI-MS (m / z): 332.25 [M+H] + .

[0075] Dissolve 29.82 g of oily compound 3 in 170 mL of acetonitrile solution, then add 6.08 g of solid methylamine hydrochloride, add 9.7 mL of diethylamine, add 0.1 mL of DMF, stir to cool down to 5 °C, add 9 mL of oxalyl chloride solution dropwise, add dropwise After the completion, the temperature was raised to 40 °C and stirred for 2 ...

Embodiment 2

[0079] Preparation of Example 2 Compound 5

[0080] Dissolve 31.2g of 1-(3-pyridylsulfonyl)-2-bromo-1H-pyrrole-3-carbonitrile in 460mL of aqueous ethanol solution (60%), add 10mL of concentrated sulfuric acid solution, heat up to 45°C, and keep the reaction for 8h, After the reaction, 500 mL of purified water was added, extracted three times with 500 mL of ethyl acetate, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was dried under reduced pressure to obtain an oily compound 3, namely 1-(3-pyridylsulfonyl)-2 -Bromo-1H-pyrrole-3-carboxylic acid, yield 87.1%, ESI-MS (m / z): 332.25 [M+H] + .

[0081] Dissolve 28.92 g of oily compound 3 in 150 mL of acetonitrile solution, then add 6.48 g of solid methylamine hydrochloride, add 9.1 mL of diethylamine, add 0.2 mL of DMF, stir to cool down to 5 °C, add 7.5 mL of oxalyl chloride solution dropwise, dropwise After the addition, the temperature was raised to 40 °C and stirred for 2 h. A...

Embodiment 3

[0083] Preparation of Example 3 Compound 5

[0084] 31.2g of 1-(3-pyridylsulfonyl)-2-bromo-1H-pyrrole-3-carbonitrile was dissolved in 160mL of ethanol aqueous solution (90%), 8mL of concentrated sulfuric acid solution was added, the temperature was raised to 60°C, and the reaction was incubated for 7h. After the reaction, 500 mL of purified water was added, extracted three times with 500 mL of ethyl acetate, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the filtrate was dried under reduced pressure to obtain an oily compound 3, namely 1-(3-pyridylsulfonyl)-2 -Bromo-1H-pyrrole-3-carboxylic acid, 87% yield, ESI-MS (m / z): 332.26 [M+H] + .

[0085] Dissolve 28.89 g of oily compound 3 in 290 mL of acetonitrile solution, then add 6.15 g of solid methylamine hydrochloride, add 11 mL of diethylamine, add 0.1 mL of DMF, stir to cool down to 5 °C, add 11 mL of oxalyl chloride solution dropwise, and complete the dropwise addition Then the temperatu...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a vonoprazan intermediate compound 5, namely N-methyl-1-(3-pyridyl sulfonyl)-2-bromo-1H-pyrrole-3-methylamine, and a preparation method of the vonoprazan intermediate compound 5. According to the method, a compound 5 can be obtained through a hydrolysis reaction, an amidation reaction and a reduction reaction by taking a compound as shown in a formula 2 as a starting material; the method is efficient in reaction, green and environment-friendly, high in yield and high in purity, and a high-quality intermediate compound is provided for preparation of vonoprazan. The invention also provides a method for preparing vonoprazan by using the compound 5, compared with the technical scheme disclosed in the prior art, the technical scheme provided by the invention avoids hydrogenation reaction with relatively high risk, the reaction route is simple and efficient, the method is safe and environment-friendly, the product purity is relatively high, and the method is suitable for industrial production.

Description

Technical field [0001] The invention belongs to the technical field of medicinal chemistry, and specifically relates to a vonoprazan fumarate intermediate and a preparation method thereof, as well as a method for using the intermediate to prepare vonoprazan fumarate. Background technique [0002] Vonoprazan fumarate, the chemical formula is 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methylamine fumarate, is A potassium ion (K + ) Competitive acid pump inhibitor (P-CAB), which has a strong and long-lasting inhibitory effect on gastric acid secretion. The metabolism of vonoprazan fumarate is less related to the liver drug enzyme CYP2C19. At the same time, vonoprazan fumarate The inhibitory effect on proton pumps does not require acid activation. The drug is absorbed at high concentrations in the target organ, the stomach, and can produce nearly maximum drug effects on the first day of administration, and this effect can last for 24 hours. Fuma The structu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D401/12C07C51/41C07C57/15
CPCC07D401/12C07C51/412C07C57/15
Inventor 褚延军提文利
Owner LUNAN PHARMA GROUP CORPORATION
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com