Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Method for preparing 5-(alpha-cyclopropyl carbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothiophene [3,2-c] pyridine

A technology of cyclopropylcarbonyl and fluorobenzyl, applied in 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydro In the field of preparation of thieno[3,2-c]pyridine, it can solve the problems of large-scale production danger, harsh reaction conditions, flammability and explosion of n-butyllithium, etc. mild effect

Inactive Publication Date: 2008-08-27
SHANGHAI INST OF PHARMA IND
View PDF1 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction conditions are very harsh, requiring a low temperature of -40°C. At the same time, n-butyllithium is flammable and explosive, which will bring danger to large-scale production.

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
  • Method for preparing 5-(alpha-cyclopropyl carbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothiophene [3,2-c] pyridine
  • Method for preparing 5-(alpha-cyclopropyl carbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothiophene [3,2-c] pyridine
  • Method for preparing 5-(alpha-cyclopropyl carbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothiophene [3,2-c] pyridine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1～2

[0039] Preparation of 5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (formula III):

[0040] 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (7.0g), potassium carbonate (7.2g) and acetonitrile (50ml) were mixed, benzyl chloride (6.1g) was added, stirred for 0.5 After 3 hours it was refluxed for 3 hours. Cool, filter, concentrate the filtrate to dryness, add ethyl acetate (30ml) and water (50ml), separate the layers, extract the aqueous layer with ethyl acetate (30ml×2), combine the organic layers, wash with water, dry, and concentrate to dryness to obtain 8.3 g of the title compound 5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine, yield 90.8%.

[0041] 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (18.0g), potassium carbonate (18.6g), benzyl chloride (15.0g), sodium iodide (0.8g) in DMF ( 100ml) was stirred for 0.5 hours, then reacted at 80°C for 3 hours, cooled, added water (150ml) and ethyl acetate (100ml), separated, and the aqueous layer was extracted with ethyl acetate (50ml×2). ...

Embodiment 3

[0043] Preparation of 2-bromo-5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (formula IV):

[0044]The compound (23.2g) obtained in Example 2 was dissolved in acetic acid (100.0ml), 40% hydrobromic acid (75.0ml), methanol (100ml), and the methanol of 30% hydrogen peroxide (33.0ml) was added dropwise under ice-water bath cooling (100ml) solution, stirred at room temperature for 3 hours. Sodium thiosulfate solution (150ml) was added dropwise, then saturated sodium carbonate solution was added dropwise until the pH was 9, extracted with dichloromethane (100ml×3), the organic layers were combined, washed with water, dried, and concentrated to dryness to obtain 30.5g of light yellow solid , yield 97.8%.

Embodiment 4～6

[0046] Preparation of 2-methoxy-5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (Formula V):

[0047] Dissolve sodium (0.43g) in methanol (20ml), add 2-bromo-5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (3.88g), bromide Cuprous (0.17g), stirred and refluxed for 12 hours. Cool, filter, concentrate the filtrate to dryness, add ethyl acetate (30ml) and water (50ml), separate the layers, extract the aqueous layer with ethyl acetate (30ml×2), combine the organic layers, wash with water, dry, and concentrate to dryness to obtain 3.3 g of oily matter was separated by column to obtain 1.3 g of the title compound, with a yield of 39.8%.

[0048] Dissolve sodium (5.6g) in methanol (120ml), concentrate to dryness, add tetrahydrofuran (100ml), 2-bromo-5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c ] Pyridine (7.5g), cuprous bromide (0.34g) and sodium iodide (0.15g), stirred and refluxed for 24 hours. Cool, filter and wash with ethyl acetate, concentrate the filtrate to dryness, add ethyl...

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 discloses a new synthesis route of 5-(alpha-cyclopropyl carbonyl-2-fluorobenzyl)-2-oxo-2, 4, 5, 6, 7, 7a-hexahydrothiophene [3, 2-c] pyridine, which only needs to one step to convert prior 2-methoxy-5-(alpha-cyclopropyl carbonyl-2-fluorobenzyl)-4, 5, 6, 7-tetrahydrothiophene [3, 2-c] pyridine hydrochloride to target compound, with mild reaction conditions, non low temperature demand, non explosive material, high yield, low cost and high efficiency. The invention is suitable for large-scale industrial production.

Description

technical field [0001] The present invention relates to the preparation of 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine method technology field. Background technique [0002] Thrombosis can cause ischemia and infarction of major organs, and can also cause edema and venous insufficiency, thereby causing various dysfunctions. Representative antithrombotic drugs currently in clinical use are clopidogrel, aspirin, and asimumab. The effect of clopidogrel is stronger than that of aspirin and has less side effects. It is clinically used to treat atherosclerosis, acute coronary syndrome, and prevent in-stent restenosis and thrombotic complications after coronary stent implantation. Prasugrel is a tetrahydrothienopyridine compound similar to clopidogrel. It has shown better activity, tolerance and safety than clopidogrel in the third phase of clinical trials, and it is expected to become a good antithrombotic drug. [0003] An importan...

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): C07D495/04
CPCY02P20/55
Inventor 吴雪松岑均达郭珩
Owner SHANGHAI INST OF PHARMA IND
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
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