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

Process for production of 5-chloro-2,4-dihydroxypyridine

A technology of dihydroxypyridine and its manufacturing method, which is applied in the fields of chemical instruments and methods, compounds of group 4/14 elements of the periodic table, organic chemistry, etc., can solve problems such as unfavorable environments, and achieve simple methods, mitigating conditions, and industrial The effect of less waste

Inactive Publication Date: 2008-01-16
TAIHO PHARMA CO LTD
View PDF3 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At this time, since a large amount of alkali is used to neutralize a large amount of acid used in the hydrolysis, a large amount of salt is generated as industrial waste, which is not preferable from an environmental point of view.

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
  • Process for production of 5-chloro-2,4-dihydroxypyridine
  • Process for production of 5-chloro-2,4-dihydroxypyridine
  • Process for production of 5-chloro-2,4-dihydroxypyridine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0066] The method for producing 5-chloro-2,4-dihydroxypyridine (1) will be described in more detail by way of examples and reference examples, but the present invention is not limited to these examples.

reference example 1

[0068] Synthesis of 5-chloro-2,2-dimethyl-1,3-dioxin-4-one

[0069] Under ice-cooling, 2.44ml (0.03mol) of sulfonyl chloride was dropped into a solution of 3.2g (0.025mol) of 2,2-dimethyl-1,3-dioxin-4-one in pyridine (16ml). Stir at room temperature for 30 minutes and at room temperature for 2 hours. The reaction solution was ice-cooled, and water was added. The reaction solution was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the dichloromethane layer was concentrated. The concentrated residue was purified by silica gel column chromatography (elution solvent n-hexane:ethyl acetate=95:5) to obtain 2.08 g of the title compound as an oily substance (yield 51.2%).

[0070] 1 H-NMR (CCl 4 )δ: 1.73(s, 6H), 7.23(s, 1H) MSm / z: 162(M + ), 164(M+2)

reference example 2

[0072] Synthesis of 5-chloro-2,2-cyclohexyl-1,3-dioxin-4-one

[0073] Under ice-cooling, 1.46ml (0.018mol) of sulfonyl chloride was dropped into a solution of 2.52g (0.015mol) of 2,2-cyclohexyl-1,3-dioxin-4-one in pyridine (13ml), and at the same temperature Stir at room temperature for 30 minutes and at room temperature for 2 hours. The reaction solution was ice-cooled, and water was added. The reaction solution was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the dichloromethane layer was concentrated. The concentrated residue was purified by silica gel column chromatography (eluting solvent n-hexane:ethyl acetate=95:5), and the resulting oily substance was crystallized from n-hexane to obtain 2.00 g of the title compound (yield 65.9%). 1 H-NMR (CDCl 3 )δ: 1.21-2.21 (m, 10H), 7.28 (s, 1H)

[0074] MSm / z: 202(M + ), 204(M+2)

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

A process for producing 5-chloro-2,4-dihydroxypyridine of Formula (1) comprising the steps of reacting a 5-chloro-1,3-dioxin-4-on derivative (2) represented by Formula (2) with a ketene acetal derivative (3) represented by Formula (3) to give a pyrone derivative (4) represented by Formula (4), treating the pyrone derivative (4) with an acid, and reacting the resulting product with ammonia: [Chemical formula 4] (1); [Chemical formula 1] (2) wherein R1 and R2 are as defined in the description; [Chemical formula 2] (3) wherein R3 and R4 independently represent a straight-chain or branched alkyl group having 1 to 6 carbon atoms or a silyl group substituted by a straight-chain or branched alkyl group having 1 to 6 carbon atoms; and [Chemical formula 3] (4) wherein R3 and R4 are as defined above. This process can produce 5-chloro-2,4-dihydroxypyridine which is an inhibitor of a biodegradation enzyme against an anti-malignant tumor agent 5-fluorouracil under mild conditions in a short process and generates less industrial waste, and therefore is industrially advantageous.

Description

technical field [0001] The present invention relates to a method for producing 5-chloro-2,4-dihydroxypyridine used as a biodegradation enzyme inhibitor of 5-fluorouracil, an anticancer agent having excellent antitumor effects, and pyrone as an intermediate for its production derivative. Background technique [0002] 5-Chloro-2,4-dihydroxypyridine (common name: gimerast) is known to enhance the antitumor effect of the antitumor agent 5-fluorouracil by inhibiting the biodegradation enzyme dihydropyrimidine dehydrogenase of the antineoplastic agent activity (refer to Patent Document 1), and the 5-fluorouracil antitumor agent (marketing name: TS-1) which is a mixture of gemimerast, tegafur (tegafur), and oxonate potassium (Oteracil potassium) has been commercially available. [0003] Conventionally, the following method is known as a method for producing 5-chloro-2,4-dihydroxypyridine. In addition, in the following description, "Ac" represents an acetyl group, and "Et" repres...

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): C07D213/69C07F7/18C07D309/32
CPCC07D309/32C07F7/1856C07D213/69C07F7/1804C07D213/62
Inventor 长泽弘志日暮胜之山中悦二
Owner TAIHO PHARMA CO LTD
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