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

A kind of preparation method of topicastat

A technology of topinostat and compounds, applied in the direction of organic chemistry, etc., can solve the problems of serious environmental pollution and large dosage, and achieve the effects of high product purity, reduced dosage, simple operation and post-treatment

Inactive Publication Date: 2016-03-30
于宗光
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] This route step is simple, although the cyanide agent zinc cyanide used is cheaper, but consumption is bigger, and the yield of cyanide step is only 66%, serious to environmental pollution

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
  • A kind of preparation method of topicastat
  • A kind of preparation method of topicastat
  • A kind of preparation method of topicastat

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: the preparation of formula (4) compound 4-(5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl)pyridine-N-oxide

[0037] Dissolve 1.20 g (0.01 mol) of 4-cyanopyridine-N-oxide (compound of formula 5) in 50 ml of methanol, then add 50 mg of sodium methoxide, and stir until dissolved. Then 1.37 g (0.01 mol) of isoniazid (compound of formula 6) was added, and heated to reflux for 10 hours. After the reaction, the precipitated solid was filtered out, washed with methanol, and then dried with a vacuum pump to obtain 1.87 g of a yellow powder product, the compound of formula (4), with a yield of 78%.

Embodiment 2

[0038] Embodiment 2: the preparation of formula (4) compound 4-(5-(pyridin-4-yl)-1H-1,2,4-triazol-3-yl)pyridine-N-oxide

[0039] Dissolve 12.0 g (0.10 mol) of 4-cyanopyridine-N-oxide (compound of formula 5) in 500 ml of methanol, then add 1.0 g of sodium methoxide, and stir until dissolved. Then, 13.7 g (0.10 mol) of isoniazid (compound of formula 6) was added, and heated to reflux for 15 hours. After the reaction, the precipitated solid was filtered out, washed with methanol and dried with a vacuum pump to obtain 18.2 g of the compound of formula (4) as a yellow powder product with a yield of 77%.

Embodiment 3

[0040] Embodiment 3: Formula (3) compound 3-(2-cyanopyridin-4-yl)-N, N-dimethyl-5-(pyridin-4-yl)-1H-1,2,4-three Preparation of azole-1-carboxamides.

[0041]With formula (4) compound 2.39g (10mmol), dimethylcarbamoyl chloride (0.22ml, 22mmol), zinc cyanide (1.40g, 12mmol), cuprous iodide 0.19g (1mmol) is dissolved in 100ml acetonitrile, the mixture React at 80°C for 5 hours, TLC detects the reaction (n-hexane / ethyl acetate=1:1), after the reaction is complete, cool to room temperature, add 100ml of water and stir for 5-30 minutes, discard the organic layer, and use the water layer Ethyl acetate was extracted three times, 100ml each time, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain the crude product, which was subjected to column chromatography with n-hexane / ethyl acetate=4:1 to obtain a pale yellow solid 2.97 g, yield 93%, HPLC purity (normalization method): 97.7%; Melting point: 112...

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 preparation method of topiroxostat, which comprises the following steps: reacting an initial raw material compound isoniazide disclosed as Formula (6) with a compound 4-cyano-pyridyl-N-oxide disclosed as Formula (5) to generate a triazole compound disclosed as Formula (4), reacting the triazole compound disclosed as Formula (4) in the presence of a copper catalyst (CuX), zinc cyanide (Zn(CN)2) and dimethylamino formyl chloride to generate a cyanotriazole compound disclosed as Formula (3), reacting the compound disclosed as Formula (3) in the presence of p-toluenesulfonic acid to generate a compound disclosed as Formula (2), and finally, alkalifying with inorganic alkali to obtain the target compound disclosed as Formula (1) (topiroxostat). The method is simple in operation and after-treatment, and greatly lowers the consumption of the zinc cyanide due to the use of the copper catalyst, so that the reaction conditions are milder, and the purity of the prepared product is high; and the method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of topicastat, which belongs to the field of medicine and chemical industry. Background technique [0002] Gout is a common disease caused by abnormal production of uric acid due to purine metabolism disorder. It has been listed by the United Nations as one of the 20 most stubborn diseases in the 21st century, and it is the second most metabolic disease after diabetes. "Hyperuricemia and Gout Treatment Chinese Expert Consensus" pointed out that the prevalence of hyperuricemia (HUA) showed an overall trend of increasing year by year, with males higher than females, and there were certain regional differences. The southern and coastal areas were economically developed. The prevalence rate in this region is higher than that in other regions in China during the same period. More importantly, the patients with HUA are showing a trend of getting younger and younger. According to statistics, the prevalence of HUA...

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): C07D401/14
CPCC07D401/14
Inventor 于宗光孙晓艳
Owner 于宗光
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