Key intermediate for preparing tedizolid phosphate, and preparation method of key intermediate

A technology of tedizolid phosphate and intermediates, applied in the field of drug synthesis, can solve the problems of potential safety hazards, impact on the quality of finished raw materials, high corrosiveness of phosphorus oxychloride, etc., and achieves simple operation, mild reaction conditions, and easy purification. Effect

Active Publication Date: 2015-05-13
CHENGDU SINO STRONG PHARMA
View PDF8 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In view of the large defects in the preparation method of tedizolid phosphate reported in the literature, it has a great impact on the quality of the finished product of the bulk drug; moreover, the phosphorus oxychloride used is too corrosive, and there is a great potential safety hazard; therefore, Designing and developing a production process with mild reaction conditions, easy operation, low cost and environment-friendly has become the focus of everyone's common attention

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
  • Key intermediate for preparing tedizolid phosphate, and preparation method of key intermediate
  • Key intermediate for preparing tedizolid phosphate, and preparation method of key intermediate
  • Key intermediate for preparing tedizolid phosphate, and preparation method of key intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 Preparation of formula I key intermediate (R=phenyl)

[0040] Add 1.1g of sodium hydride and 50mL of dry tetrahydrofuran into a 100mL round-bottomed flask in sequence, and drop 5g of the dry tetrahydrofuran solution of the compound of formula II into the reaction flask under the conditions of ice bath and nitrogen protection. The reaction was stirred at room temperature for 5 hours; subsequently, 11 g of tetrabenzyl pyrophosphate was added to the reaction liquid in batches, and the reaction was stirred at room temperature for 10 hours.

[0041] TLC detects that the reaction is complete. Slowly add ice water to the reaction solution to quench the reaction, extract with ethyl acetate, separate layers, dry and concentrate the organic layer, and recrystallize the residue with ethyl acetate / petroleum ether to obtain about 7 g of a light yellow solid, yield: 82 %. 1 H-NMR (CDCl 3 ,400MHz): δ=8.92(s,1H),8.30(d,J=8.0Hz,1H),8.04~8.02(m,1H),7.55~7.45(m,2H),7.36~7.2...

Embodiment 2

[0042] Example 2 Preparation of tedizolid phosphate

[0043] 3g of the key intermediate of formula I (R=phenyl), 0.3g of Pd / C, and 30mL of methanol were sequentially added into a 50mL round-bottomed flask, and stirred for about 6 hours under hydrogen gas at room temperature. TLC monitored the completion of the reaction. Add sodium hydroxide solution to the reaction to adjust the pH of the reaction solution to 9-10, filter, wash the filter cake with water, and collect the filtrate.

[0044] Under stirring conditions, the pH of the solution was adjusted to 2-3 with hydrochloric acid, and a solid was precipitated. Filtrate, wash with water, collect the solid, and recrystallize to obtain about 1.5 g of a white solid, yield: 71%. 1 H-NMR (d 6 -DMSO, 400MHz): δ=8.94(s,1H), 8.24~8.18(m,2H), 7.78~7.68(m,2H), 7.53~7.50(m,1H), 4.96~4.95(m,1H) ,4.48(s,3H),4.23(t,J=8.0Hz,1H),4.14~4.02(m,2H),3.94~3.90(m,1H)ppm; HRMS-ESI(m / z):451.0930( M+H + ).

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 key intermediate for preparing tedizolid phosphate. The key intermediate has a structure shown in formula I: R is any one of R1 or R2, and the R1 and R2 are independently selected from aryl groups or replaced aryl groups. The invention further discloses a preparation method of the key intermediate, and a method for preparing tedizolid phosphate by the key intermediate. The key intermediate disclosed by the invention is a solid compound and is easy to purify; besides, dipolymers, multimers and hydrolysis impurities cannot be generated during the preparation of tedizolid phosphat, the reaction temperature is moderate, the operation is simple, a strong-acidity reagent (phosphorus oxychloride) is prevented from being used, and the preparation method belongs to an environment-friendly production technology.

Description

technical field [0001] The invention relates to a key intermediate for preparing tedizolid phosphate and a preparation method thereof, belonging to the field of drug synthesis. Background technique [0002] Tedizolid phosphate, (R)-(3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl) -2-oxooxazolidin-5-yl) methyl dihydrogen phosphate, is a drug applied by Cubist for the treatment of acute bacterial skin and skin tissue infections, FDA has approved it in 2014 Approved for listing on June 20, 2010, the trade name is SIVEXTRO. Tedizolid phosphate belongs to the second-generation oxazolidinone antibiotics. According to phase III clinical trial data, its clinical effect is comparable to that of linezolid, and its adverse reactions in gastrointestinal tract and thrombocytopenia are less than linezolid. It also has a lower incidence of drug toxicity and has a longer half-life, making it a reasonable alternative to linezolid. [0003] At present, there are few litera...

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): C07F9/6558
Inventor 张善军关文捷杨磊匡建明高建曾梅
Owner CHENGDU SINO STRONG PHARMA
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