Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Avanafil preparation method

An avanafil and compound technology, which is applied in the field of drug synthesis, can solve the problems of low product purity, low reaction yield, complicated operation, etc., and achieves the advantages of reducing production cost, simple operation, and improving reaction yield and product purity. Effect

Inactive Publication Date: 2015-04-22
NANJING XIAOZHUANG UNIV
View PDF3 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the preparation method has the disadvantage of high cost
[0016] In addition to the above cost factors, the preparation method of patent CN201210006859.4 also has disadvantages such as complex operation, low product purity, and low reaction yield.

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
  • Avanafil preparation method
  • Avanafil preparation method
  • Avanafil preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] first hydrolysis

[0037] Its reaction formula is as follows:

[0038]

[0039] Add 5g of compound 2 (sulfide) into a three-necked flask, add 50g of water, add 27% sodium hydroxide solution dropwise at room temperature (20°C), raise the temperature to 90°C, and heat until it dissolves. After 3.5 hours, the solution cleared and the system was light yellow. Cool down to room temperature (20°C), adjust the pH to 4.0 with 10% hydrochloric acid, share 6g of 10% hydrochloric acid (the initial pH value is around 12.5), filter with suction after the pH is stable, wash with 25ml of water for 3 Wash once with 20ml ethanol, dry in vacuum at 45°C until the water content is <0.1%. See Table 2 for the raw materials and the feeding amount of this step.

[0040] Table 2

[0041] name

[0042] second condensation

[0043] Its reaction formula is as follows:

[0044]

[0045]Add 15g of compound 6 (hydrolyzed acid) into a single-necked flask, add 150ml of toluene, 12g...

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 relates to an avanafil preparation method. The method comprises the steps that a hydrolysis reaction is carried out on 4-(3-chlorin-4-methoxy benzyl amino)-2-methylehio pyrimidine-5-carboxylic acid ethyl ester, namely a compound (2) to obtain 4-(3-chlorin-4-methylehio pyrimidine)-2-methylehio pyrimidine-5-carboxylic acid, namely a compound (6); an acylation reaction is carried out on the compound (6) and thionyl chloride, and then the product and 2-sulfadoxine-pyrimethamine or a salt of 2-sulfadoxine-pyrimethamine are condensed to obtain 4-(3-chlorin-4-methylehio pyrimidine)-2-methylehio pyrimidine-N-(2- pyrimidine methyl)-5-pyrimidine formamide, namely a compound (7); the compound (7) is oxidized by metachloroperbenzoic acid to obtain 4-(3-chlorin-4-methylehio pyrimidine)-2-methylsulfonyl pyrimidine-N-(2-pyrimidine methyl)-5-pyrimidine formamide, namely a compound (8), a nucleophilic substitution reaction is carried out on the compound (8) and L-prolinol to obtain avanafil. The method is low in cost, easy and convenient to operate, high in product purity, high in reaction yield and suitable for industrialization scale production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a synthesis method of avanafil. Background technique [0002] Avanafil (Avanafil, trade name is Stendra) is a drug developed by Vivus Company of the United States authorized by Mitsubishi Pharmaceutical Co., Ltd. of Japan for the treatment of male erectile dysfunction. It was approved by the FDA in the United States on April 27, 2012. listed. Avanafil is an oral fast-acting highly selective phosphodiesterase-5 (PDE-5) inhibitor, which is the product with the fastest effect and the least side effects among similar drugs for the treatment of erectile dysfunction (ED). Avanafil (compound 1) Chinese chemical name: (S)-4-(3-chloro-4-methoxybenzylamino)-2-(2-hydroxymethyl-1-pyrrolidinyl)-N- (2-pyrimidinemethyl)-5-pyrrolidinylcarboxamide; English chemical name: (S)-4-[(3-chloro-4-methoxybenzyl)amino]-2-(2-hydroxymethyl-1-pyrrolidinyl)-N -(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide; mo...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/14
CPCC07D403/14
Inventor 周宏张辉于姗姗刘少贤袁国军
Owner NANJING XIAOZHUANG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com