Synthesis method of key intermediate 2-cyanpyrazine of tuberculosis drug pyrazinamide

A technology of pyrazinamide and cyanopyrazine is applied in the field of synthesizing 2-cyanopyrazine, an intermediate of anti-tuberculosis drug pyrazinamide, and can solve the problems of harsh conditions, low yield, high temperature and high pressure conditions, etc. Post-processing simple effects

Inactive Publication Date: 2008-10-22
ZHEJIANG UNIV
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The preparation of catalysts in the above synthesis processes is complex, the reaction process cycle time is long, the conditions are harsh, or many experimental processes involve high temperature and high pressure conditions, low yield, complex post-processing and other problems

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
  • Synthesis method of key intermediate 2-cyanpyrazine of tuberculosis drug pyrazinamide
  • Synthesis method of key intermediate 2-cyanpyrazine of tuberculosis drug pyrazinamide
  • Synthesis method of key intermediate 2-cyanpyrazine of tuberculosis drug pyrazinamide

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0015] The specific reaction steps of the synthetic method of the key intermediate 2-cyanopyrazine of anti-tuberculosis drug pyrazinamide are as follows:

[0016] Alkylbenzene is used as the reaction solvent, cuprous iodide, potassium iodide and N, N'-dimethylethylenediamine are used as the combined catalyst, and 2-bromopyrazine and sodium cyanide are reacted at 100-150°C under the protection of nitrogen After 20 to 48 hours, it was filtered, and the filtrate was fractionated under reduced pressure to obtain 2-cyanopyrazine with high yield and high purity. Wherein the molar equivalent ratio of 2-bromopyrazine and sodium cyanide is 1: 1.0~2.0; The consumption of cuprous iodide is 5~30% molar equivalent of 2-bromopyrazine; 1.5-3 molar equivalents; the amount of N,N'-dimethylethylenediamine is 1-1.5 molar equivalents of 2-bromopyrazine. The recommended reaction solvent alkylbenzene is toluene, ethylbenzene, xylene, and toluene is the most preferred. The recommended response tim...

Embodiment 1

[0019] In a 1-liter three-necked flask, 500 milliliters of toluene, 48 grams (0.3 moles) of 2-bromopyrazine, 11.8 grams (0.36 moles, 1.2 equivalents) of sodium cyanide, 5.73 grams (30 millimoles, 0.1 Equivalent) cuprous iodide, 10 grams of potassium iodide (60 millimoles, 0.2 equivalents), 26.4 grams of N, N'-dimethylethylenediamine (0.3 moles, 1.0 equivalents), under nitrogen protection at 110 ° C stirring reaction for 30 Hours, the reaction was terminated, followed by filtration, and the filtrate was fractionated under reduced pressure to obtain transparent liquid 2-cyanopyrazine with a yield of 70%, a purity of 99% (GC), and a boiling point of 84-87°C (18-20mmHg).

Embodiment 2

[0021] In a 1-liter three-necked flask, 500 milliliters of ethylbenzene, 48 grams (0.3 moles) of 2-bromopyrazine, 11.8 grams (0.36 moles, 1.2 equivalents) of sodium cyanide, 5.73 grams (30 mmoles, 0.1 equivalent) cuprous iodide, 10 grams of potassium iodide (60 millimoles, 0.2 equivalents), 26.4 grams of N, N'-dimethylethylenediamine (0.3 moles, 1.0 equivalents), stirred at 120 ° C under nitrogen protection After 25 hours, the reaction was completed, followed by filtration, and the filtrate was fractionated under reduced pressure to obtain transparent liquid 2-cyanopyrazine with a yield of 73% and a purity of 99%.

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 synthesizing method of 2-cyano pyrazine as key intermediate of antitubercular drugs aldinamide, which comprises the following steps: adopting alkyl benzene as reacting solvent; making 1.5-3% cuprous iodide, potassium iodide and 1-1.5% N, N'-dimethyldiamine as composite catalyst; reacting 2, 2-difluobromobenzene and sodium cyanide with molar rate at 1: 1.0-2.0 protected by nitrogen at 100-150 Deg C for 20-48h; filtering; decompressing the filtrate; fractioning to obtain the product. The invention shortens reacting flow path, which is simple to feed and dispose.

Description

technical field [0001] The invention relates to a method for preparing a pharmaceutical intermediate, in particular to a method for synthesizing an anti-tuberculosis drug pyrazinamide intermediate 2-cyanopyrazine. Background technique [0002] 2-cyanopyrazine is an important raw material for the production of pyrazinamide, a drug for treating tuberculosis. Therefore, how to efficiently synthesize 2-cyanopyrazines has attracted great attention. The synthesis of 2-cyanopyrazine has been reported in some literatures. For example, the literature "Fine Chemical Industry" reported the research on the preparation of 2-cyanopyrazine by ammoxidation of 2-methylpyrazine with a special catalyst. The literature Applied Catalsis, 1986, 20: 219-222 reported that ethylenediamine and propylene glycol were cyclized, dehydrated and dehydrogenated to 2-methylpyrazine under the action of a catalyst, and then catalyzed by high temperature and high pressure for ammoxidation to 2-cyanopyrazine. ...

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 Patents(China)
IPC IPC(8): C07D241/24
Inventor 徐方羲林旭锋
Owner ZHEJIANG UNIV
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