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

Method for purifying cangrelor intermediate

A purification method and intermediate technology, applied in organic chemistry methods, chemical instruments and methods, organic chemistry, etc., can solve the problems of cumbersome operation of purification methods, unsuitable scale-up production, high equipment requirements, etc., and achieve short reaction time and low production cost The effect of low, high product purity

Active Publication Date: 2017-05-17
上海云晟研新生物科技有限公司
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to overcome the cumbersome operation of the purification method of cangrelor intermediate I in the prior art, the use of expensive ion exchange resins for purification, the need to use freeze-drying, high equipment requirements, low production capacity, and no A purification method for cangrelor intermediates is provided because it is suitable for defects such as scale-up 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 purifying cangrelor intermediate
  • Method for purifying cangrelor intermediate
  • Method for purifying cangrelor intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Embodiment 1: the preparation method of cangrelor intermediate I crude product

[0047]

[0048] 5g of cangrelor intermediate III and 3.42g of 1,8-bisdimethylaminonaphthalene were dissolved in 106g of triethyl phosphate, cooled to 0°C in an ice bath, and 3.27g of phosphorus oxychloride was added dropwise to the reaction solution. The reaction was carried out at 0° C. for 6 hours, and TLC detected that the reaction of the cangrelor intermediate III was complete. A solution of crude cangrelor intermediate I in triethyl phosphate (HPLC purity about 75%) was obtained.

Embodiment 2

[0049] The purification method of embodiment 2 cangrelor intermediate I crude product

[0050] The triethyl phosphate solution of the crude cangrelor intermediate I (HPLC purity about 75%, which can be prepared in Example 1) was poured into 300 mL of ice water containing 13.6 g of sodium bicarbonate, and stirred for 1 hour. The aqueous phase was extracted with diethyl ether (3 x 350 mL) and the organic phase was discarded. The aqueous phase was concentrated under reduced pressure (-0.08MPa~-0.1MPa) at 40°C until no fraction evaporated. 100 ml of ethanol was added to the residue and stirred for 2 hours. The precipitated solid was filtered and washed with 10 mL of ethanol. The obtained solid was redissolved in 80 ml of deionized water, adjusted to pH 2-3 with 1N hydrochloric acid, stirred for 1 hour, filtered, and the obtained solid was washed with 5 ml of deionized water. Dissolve the above solid in 50ml of ethanol, add 5ml of ammonia water with a mass concentration of 25% (...

Embodiment 3

[0051] Embodiment 3: the preparation method of cangrelor intermediate I crude product

[0052] Put 15Kg of cangrelor intermediate III and 10.3Kg of 1,8 bis-dimethylaminonaphthalene into 300Kg of triethyl phosphate, cool the frozen brine to 0-5°C, and drop 9.9Kg of phosphorus oxychloride into the reaction solution. Stir at 0-5°C for 8 hours, TLC detects that the reaction of cangrelor intermediate III is complete. A triethyl phosphate solution of the crude cangrelor intermediate I was obtained, with an HPLC purity of about 90%.

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 method for purifying a cangrelor intermediate. The invention provides a method for purifying a cangrelor intermediate I; the method comprises the steps of 1, mixing a cangrelor intermediate I crude product with an organic solvent to form a mixture, enabling the mixture to react with basic salt or ammonia water, and then extracting to obtain a water phase; 2, removing water in the water phase, then adding an alcohol solvent into the water phase, and filtering or centrifuging to obtain a filter cake; 3, adjusting the pH of the obtained filter cake to 2-3 in water, and filtering or centrifuging to obtain another filter cake; 4, adjusting the pH of the obtained filter cake to 7-8 in the alcohol solvent, and filtering to obtain the cangrelor intermediate I. The method for purifying the cangrelor intermediate does not adopt a reverse silica gel separation method and cation exchange resin which is expensive, cumbersome in operation and long in purification time; the method is simple in operation, short in reaction time, high in yield and high in purity of a prepared product; after the method is used, the high performance liquid chromatography (HPLC) purity is more than 99.0%; the method is low in production cost and suitable for industrial production. The structural formula of the cangrelor intermediate I is described in the description.

Description

technical field [0001] The invention relates to a method for purifying a cangrelor intermediate. Background technique [0002] Cangrelor (Cangrelor, II) is an intravenous small-molecule P2Y12 inhibitor that can rapidly aggregate and can reduce the risk of thrombotic cardiovascular disease. In the United States, about 500,000 people undergo PCI (percutaneous coronary intervention) every year. Cangrelor can reduce the serious blood clotting complications associated with the intervention, including heart attack and stent thrombosis, by preventing platelet aggregation. The Division of Cardiovascular and Renal Medicines in the FDA's Center for Drug Evaluation and Research believes the approval of cangrelor may provide another treatment option for patients undergoing PCI in which blood clotting can cause serious problems. The European Committee for Medicinal Products for Human Use (CHMP) recommends approval of cangrelor for adult patients undergoing PCI. The US FDA announced on ...

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): C07H19/20C07H1/06
CPCC07B2200/07C07H1/06C07H19/20
Inventor 应述欢皮红军汪仙阳陈健
Owner 上海云晟研新生物科技有限公司
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