Process for preparation of heterocyclic derivative compounds, compositions containing compounds, and hydrates of compounds

A technology of compounds and hydrates, which can be used in drug combinations, organic chemical methods, and medical preparations containing active ingredients, etc., can solve problems such as high price and induced gene mutation, and achieve excellent results in uric acid-related diseases.

Pending Publication Date: 2022-02-25
JW PHARMA CORP
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] In addition, the starting material 3,5-dibromo-4-methoxy-benzoyl chloride having the following structure as the compound of the [chemical formula III] in the production method is 3,5-dibromo-4 - The price of methoxybenzoic acid is expensive, and there is a possibility of inducing gene mutation during the synthesis of the compound of [chemical formula III] and the oxazine derivative of [chemical formula IV], so a process that can minimize it is required

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 preparation of heterocyclic derivative compounds, compositions containing compounds, and hydrates of compounds
  • Process for preparation of heterocyclic derivative compounds, compositions containing compounds, and hydrates of compounds
  • Process for preparation of heterocyclic derivative compounds, compositions containing compounds, and hydrates of compounds

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0077] The preparation method of the compound of chemical formula I, its salt or hydrate

[0078] The present invention relates to the preparation method of the compound of chemical formula I, its pharmaceutically acceptable salt or its hydrate, comprising the step of coupling the compound of the following chemical formula III with the compound of the following chemical formula IV.

[0079] [Reaction 1]

[0080]

[0081] In the formula, R is hydrogen or Boc.

[0082] Specifically, a base is added to the compound of the chemical formula III, and the compound 3,4-dihydro-2H-pyrido[4,3-b][1,4]oxazine hydrobromide (2HBr ) for the coupling reaction. The obtained intermediate compound is post-treated to obtain the compound (3,5-dibromo-4-hydroxyl phenyl) (2,3-dihydro-4H-pyrido[4,3-b][ 1,4] oxazin-4-yl)-methanone or a pharmaceutically acceptable salt thereof.

[0083] In a specific embodiment of the present invention, the compound of the chemical formula III can be obtained ...

Embodiment 1

[0169] Synthesis of compound 3,4-dihydro-2H-pyrido[4,3-b][1,4]oxazine hydrobromide (2HBr) of chemical formula IV become

[0170] (1) Preparation of 4-chloro-3-nitropyridine

[0171] 50g (0.356mmol) of 4-hydroxyl-nitropyridine was stirred in 50mL (1T) of DMF (dimethylformamide) and 450mL (9T) of ethyl acetate, and 42.5mL of phosphorus oxychloride ( POCl 3 , 1.3eq), heated up and heated to reflux at 70-80°C for 2 hours. After the reaction, the reaction solution was cooled to 40° C., and 200 mL of water was added to terminate the reaction. The separated organic layer was washed with 200 mL of saturated sodium bicarbonate (NaHCO 3 ), 200 mL of brine (brine), and the collected organic layer was washed with magnesium sulfate (MgSO 4 ) was dried and filtered, then concentrated under reduced pressure to obtain 60 g of light yellow concentrated crystal 4-chloro-3-nitropyridine.

[0172] (2) Preparation of 2-((3-nitropyridin-4-yl)oxy)methyl acetate

[0173] 60g (0.356mmol) of ...

Embodiment 2

[0184] The compound of chemical formula I (3,5-dibromo-4-hydroxyphenyl) (2,3-dihydro-4H-pyrido[4,3-b][1,4]oxa Synthesis of oxazin-4-yl)-methanone

[0185] At 25-30°C, add 1L of tetrahydrofuran (THF) to the reactor, add 139g (0.470mol) of 3,5-dibromo-4-hydroxybenzoic acid, and then add 278g (1.27mol) to the reactor of di-tert-butyl dicarbonate. Add 125g (1.58mol) of pyridine under a nitrogen atmosphere, and stir the reaction solution for 2 hours at 25-30°C to obtain 3,5-dibromo-4-tert-butoxycarbonyloxy-benzoic acid and 3 , The reaction solution of 5-dibromo-4-((tert-butoxycarbonyl)oxy)benzoic acid (tert-butylcarbonyl) anhydride.

[0186] At a temperature of 25 to 30°C, 170 g (1.68 mol) of triethylamine was added to the reaction liquid, and 100 g of 3,4-dihydro-2H prepared in Example 1 was added to the reaction liquid - Pyrido[4,3-b][1,4]oxazine hydrobromide (2HBr), the reaction solution was stirred for 6 hours at a temperature of 25-30°C. Remove the formed salt and colle...

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 novel preparation method of a heterocyclic derivative compound of a chemical formula I; a novel intermediate compound for use in the preparation process; and a composition for treating or preventing hyperuricemia, gout disease, nephritis, chronic renal failure, kidney stone, uremia, lithangiuria or uric acid-related diseases. The composition comprises a compound of formula I in an administration dose of more than 2 mg to 10 mg or less, orally administered once a day. The invention also discloses a hydrochloride 1.5 hydrate of the novel compound of the chemical formula I.

Description

[0001] The application date is May 24, 2018, the Chinese patent application number is 201880034458.5 and the title of the invention is "Preparation method of heterocyclic derivative compound, composition containing the compound and hydrate of the compound" in China A divisional application of a patent application, and this application claims priority from Korean application No. 10-2017-0064914. technical field [0002] The present invention relates to a new preparation method of a heterocyclic derivative compound of the following chemical formula I; a new intermediate compound used in the preparation method; for the treatment or prevention of hyperuricemia, gout, nephritis, chronic renal failure, Compositions for kidney stones, uremia, urolithiasis, or uric acid-related diseases, said compositions comprising a compound of formula I administered orally once a day at an administration dose of more than 2 mg to less than 10 mg; and novel salts of compounds of formula I salt 1.5 h...

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): C07D498/04A61K31/5383A61P19/06A61P13/12C07C69/96
CPCC07D498/04A61K31/5383A61P19/06A61P13/12C07C69/96C07B2200/13A61K9/20A61K9/1682
Inventor 片道圭吴景珍
Owner JW PHARMA CORP
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