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

Preparation method for novel SGLT2 inhibitor medicine

An inhibitor and drug technology, applied in organic chemistry and other directions, can solve the problems of long synthetic process route, difficult solidification and purification treatment of intermediates, complicated preparation process, etc., and achieves easy quality control, low production cost and high reaction yield. Effect

Active Publication Date: 2015-09-23
NANTONG CHANGYOO PHARMATECH CO LTD
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In order to solve the existing problems in the preparation of canagliflozin such as long synthetic process route, cumbersome preparation process, difficult solidification and purification treatment of intermediates, and yield of the synthetic route, the present invention provides a new, short synthetic process route, intermediate Canagliflozin preparation scheme with easy body weight control and high reaction yield

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
  • Preparation method for novel SGLT2 inhibitor medicine
  • Preparation method for novel SGLT2 inhibitor medicine
  • Preparation method for novel SGLT2 inhibitor medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] (1). Preparation of gluconolactone intermediate

[0035] Add 500mL of toluene to the reaction flask, start stirring, add 50g of D-gluconolactone and 5g of piperidine, cool down to -5~0℃, add 30mL of N-methylpyrrolidone, control the temperature at -5~0℃, then drop Add 33.5g of acetyl chloride, and control the temperature at -5~0°C; after dropping, raise the temperature to 20-25°C, and stir overnight. After the reaction, cool down to -5~0°C, add 200mL saturated sodium bicarbonate solution, stir, let stand to separate the liquid, extract the water layer once with 300mL toluene, combine the organic phases, wash with 500mL water, and then use 300mL saturated chlorinated Wash with aqueous sodium solution, dry over anhydrous sodium sulfate, filter with suction, and concentrate the organic phase under reduced pressure to obtain 80.2 g of an oily product. The yield is 93.5%.

[0036] (2). Preparation of 2-(5-bromo-2-methylbenzoyl)-5-(4-fluorophenyl)thiophene

[0037] ...

Embodiment 2

[0045] (1). Preparation of gluconolactone intermediate

[0046] Add 700mL of dichloromethane into the reaction bottle, start stirring, add 50g of D-gluconolactone and 10g of triethylamine, cool down to -5~0°C, add 20mL of N-methylpyrrolidone, and control the temperature at -5~0°C , and then dropwise added 38.9g of methanesulfonyl chloride, temperature controlled -5~0°C; after dropping, the temperature was raised to 20-25°C, and stirred overnight. After the reaction, cool down to -5~0°C, add 300mL saturated sodium bicarbonate solution, stir, let stand for liquid separation, extract the water layer once with 500mL dichloromethane, combine the organic phases, wash with 500mL water, and then wash with 500mL saturated Wash with aqueous sodium chloride, dry over anhydrous sodium sulfate, filter with suction, and concentrate the organic phase under reduced pressure to obtain 81.5 g of an oily product. Yield 95.2%.

[0047] (2). Preparation of 2-(5-bromo-2-methylbenzoyl)-5-(...

Embodiment 3

[0056] (1). Preparation of gluconolactone intermediate

[0057] Add 500mL ether into the reaction flask, start stirring, add 40g D-gluconolactone and 6gDMAP, cool down to -5~0℃, add 10mL N-methylpyrrolidone, control the temperature at -5~0℃, and then add dropwise 38.9 g acetyl chloride, temperature control -5~0°C; after dropping, raise the temperature to 20-25°C, and stir overnight. After the reaction, cool down to -5~0°C, add 200mL saturated sodium bicarbonate solution, stir, let stand for liquid separation, extract the water layer once with 300mL ether, combine the organic phases, wash with 500mL water, and then use 500mL saturated chlorinated Wash with aqueous sodium solution, dry over anhydrous sodium sulfate, filter with suction, and concentrate the organic phase under reduced pressure to obtain 63.6 g of an oily product. Yield 95.2%.

[0058] (2). Preparation of 2-(5-bromo-2-methylbenzoyl)-5-(4-fluorophenyl)thiophene

[0059] Add 30g of 5-bromo-2-methylben...

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 preparation method for novel SGLT2 inhibitor medicine. The preparation method includes the steps that D-gluconolactone serves as an initial raw material and reacts with an acylation reagent under the action of a base to obtain a glucolactone intermediate with hydroxyl protection; 5-bromine-2-methyl benzoic acid is prepared into an acid chloride through an acylation reagent, and the acid chloride and 2-(4-fluoro-phenyl) thiophene perform friedel-Crafts acylation reaction under the action of Lewis acid; 2-(5-bromine-2-methyl-benzoyl)-5-(4-fluoro-phenyl) thiophene and the glucolactone intermediate perform electrophilic substitution reaction under the action of super-strong bases, and then etherification reaction is performed to obtain methyl etherate; the methyl etherate restores carbonyl into methylene under the action of a reducing agent, and an methoxy group is removed to form an S-configuration aromatic gluconolactone intermediate; the aromatic gluconolactone intermediate is hydrolyzed under the action of a base to obtain a canagliflozin product. The synthesis process route is short and simple, the quality of the intermediate is easy to control, the reaction yield is high, the production cost is low, and the preparation method is suitable for industrialized production.

Description

technical field [0001] The invention relates to a preparation method of a novel SGLT2 inhibitor drug, in particular to a preparation method of canagliflozin. Background technique [0002] Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia due to defects in insulin secretion and / or insulin action. According to the International Diabetes Federation (IDF), 382 million people worldwide had diabetes in 2013, and 316 million people with impaired glucose tolerance (IGT) were at high risk of developing diabetes. The incidence of diabetes is on the rise due to the expansion of the global obesity population, and without intervention, its number may increase to 471 million by 2035. Since the discovery of insulin by Banting et al. in Canada in 1921 and its successful clinical use, diabetes has been well treated and controlled, and more than 40 antidiabetic drugs have been approved for the treatment of diabetes. It cannot be completely cured, and the needs of ...

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
IPC IPC(8): C07D409/10
CPCC07D409/10
Inventor 李泽标胡海洋丁海明顾文超毛青严军
Owner NANTONG CHANGYOO PHARMATECH 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