Synthetic method of prasugrel

A synthesis method and compound technology, applied in the field of synthesis of medicinal compounds, can solve the problems of slow reaction speed, low purity of condensation products, increased synthesis cost, etc., and achieve the effects of fewer by-products, fewer reaction steps and higher yields

Active Publication Date: 2014-07-16
广东暨大基因药物工程研究中心有限公司
View PDF5 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The defect of the above method is that the key condensation reaction reaction rate is slow for 24 hours, and the obtained condensation product has low purity, and the yield is only about 30%.
Moreover, the synthesis of the intermediate 2-oxo-2,4,5,6,7,7α-hexahydrothieno[3,2-c]pyridine (5) has undergone two steps of protection and deprotection, greatly increasing the synthetic cost

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
  • Synthetic method of prasugrel
  • Synthetic method of prasugrel
  • Synthetic method of prasugrel

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0017] 1-cyclopropyl-2-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-2-(2-fluorobenzyl)ethanone hydrobromide

[0018]

[0019] Add 40 mL of acetonitrile and 6.76 g (38.9 mmol) of 4,5,6,7-tetrahydrothieno[3,2-c]-pyridine hydrochloride into a 100 mL two-necked flask, and add 20.0 g of potassium bicarbonate ( 0.2mol). After reacting for 30 minutes, a mixture of 10.03 g (39.0 mmol) of 2-bromo-1-cyclopropyl-(2-fluorophenyl)ethanone and 10 mL of acetonitrile was added dropwise, and the dropwise was completed in about 30 minutes. The reaction was carried out at room temperature for 25 hours, and the reaction was monitored by TLC. Filter off the solid, wash with 10mL of acetonitrile, then remove the solvent under reduced pressure at 50°C, add 20mL of acetone to the residue, cool to 10°C, add 6.5mL of 48% hydrobromic acid aqueous solution dropwise at this temperature, and dropwise add Precipitation was observed upon completion and stirring was continued for 3 hours at room temperature....

example 2

[0020] Example 21-Cyclopropyl-2-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-2-(2-fluorobenzyl)ethanone hydrobromide

[0021] Add 40mL of acetonitrile and 6.76g (38.9mmol) of 4,5,6,7-tetrahydrothieno[3,2-c]-pyridine hydrochloride into a 100mL two-necked flask, and add 27.6g of potassium carbonate (0.2 mol). After reacting for 30 minutes, a mixture of 10.03 g (39.0 mmol) of 2-bromo-1-cyclopropyl-(2-fluorophenyl)ethanone and 10 mL of acetonitrile was added dropwise, and the dropwise was completed in about 30 minutes. The reaction was carried out at room temperature for 25 hours, and the reaction was monitored by TLC. Filter off the solid, wash with 10mL of acetonitrile, then remove the solvent under reduced pressure at 50°C, add 20mL of acetone to the residue, cool to 10°C, add 6.5mL of 48% hydrobromic acid aqueous solution dropwise at this temperature, and dropwise add Precipitation was observed upon completion and stirring was continued for 3 hours at room temperature. Cool to ...

example 35

[0022] Example 35-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine hydrobromide

[0023]

[0024] Add 15.70g (50.0mmol) 1-cyclopropyl-2-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-2-( 2-fluorobenzyl)ethanone (20.0g compound with KHCO 3 solution free) and 60mL of anhydrous tetrahydrofuran, 34mL (2.2mol / L, 75mmol) n-butyllithium / n-hexane solution was added dropwise under stirring at 0°C, after stirring for 2 hours, cooled to -10°C, and 20.0mL ( 75mmol) a mixture of tributyl borate and 50mL tetrahydrofuran was reacted at -10°C for 1 hour, then further cooled to -20°C, 3.0mL (0.10mol) of 30% hydrogen peroxide was added dropwise, and the temperature was raised to room temperature and stirred for 12 hours. Extract with ethyl acetate (100mL×2), combine the organic layers, wash with water (100mL×3), dry over anhydrous sodium sulfate, spin dry the solvent under reduced pressure at 50°C, dissolve the mixture in 40mL acetone, cool to 10°C, at this...

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 a synthetic method of prasugrel. 2-bromo-1-cyclopropyl-2-(2-fluorophenyl) acetone and 4,5,6,7-tetrahydro thieno [3,2-C] pyridine hydrochloride are condensed under the action of alkali, so that an intermediate, namely 1-cyclopropyl-2-(6,7-dihydro thieno [3,2-C] pyridine-5(4H)-yl)-2-(2-fluorophenyl) acetone, is obtained, and then oxidation and acylation are carried out, so that prasugrel is obtained. The synthetic method of prasugrel has the advantages that a prasugrel intermediate is synthesized, condensation yield is high, operating steps are simple, protection and deprotection steps in the prior art are eliminated, and cost is greatly saved.

Description

technical field [0001] The present invention relates to a synthetic method of a medicinal compound, in particular to a synthetic method of prasugrel. Background technique [0002] Prasugrel (compound 1, prasugrel), the chemical name is 2-acetoxy-5-(α-cyclopropylcarbonyl-2'-fluorophenyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine. Prasugrel is a third-generation thienopyridine derivative, which was first launched in Europe in February 2009, and is a new generation of oral anti-platelet aggregation inhibitors. [0003] [0004] Existing industrialized process takes cyclopropylcarbonyl-2-fluorobenzene (compound 6) as starting material, reacts with bromine or NBS to obtain α-cyclopropylcarbonyl-2-fluorobenzyl bromide (compound 7), and then Potassium carbonate was used as an acid-binding agent to react with 2-oxo-2,4,5,6,7,7α-hexahydrothieno[3,2-c]pyridine (compound 5) to generate 5-(α-cyclopropyl Carbonyl-2-fluorophenyl)-2-oxo-2,4,5,6,7,7α-tetrahydrothieno[3,2-c]pyridine (co...

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): C07D495/04
CPCC07D495/04
Inventor 张庆华徐广宇陈波
Owner 广东暨大基因药物工程研究中心有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap