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

Industrial production method of linagliptin

A production method and intermediate technology, applied in the field of industrial production of linagliptin, can solve the problems of low purity of intermediates, large environmental pollution, complicated operation, etc., and achieve good impurity removal effect, good repeatability, and high purity Effect

Inactive Publication Date: 2016-10-12
合肥远志医药科技开发有限公司
View PDF5 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the purity of the intermediates in the current industrialized preparation method is not high, the operation is complicated, the cost is high, and the environmental pollution is large.

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
  • Industrial production method of linagliptin
  • Industrial production method of linagliptin
  • Industrial production method of linagliptin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] 1. Preparation of Intermediate I:

[0018] Add dipolar aprotic organic solvent N-methylpyrrolidone 32kg, anhydrous potassium carbonate 4kg, 8-bromo-7-(2-butyne)-3-methylxanthine 2.8kg, 2-chloromethyl-4- Methyl-quinazoline 4kg, potassium iodide 0.78kg, stir, heat up to 75°C and insulate and stir for 3hr, detect 8-bromo-7-(2-butyne)-3-methylxanthine raw material residue is no more than 1.0% stop, Cool down to below 40°C, add 48kg of purified water dropwise at a constant speed under stirring, continue to cool down and cool to 15°C, keep stirring for 2 hours, centrifuge, and rinse the solid with 15kg of purified water to obtain a khaki-yellow wet product, which is placed in a double-cone dryer for 50 ℃ and dried under reduced pressure (-0.09Mpa) for about 18hr until the weight loss on drying was no more than 1.0%, and 5.5kg of intermediate I was obtained as a khaki-yellow dry product, with a purity of 98.8% and a yield of 90%. The structural formula of intermediate I was as...

Embodiment 2

[0027] 1. Preparation of Intermediate I:

[0028] Add dipolar aprotic organic solvent N-methylpyrrolidone 29kg, anhydrous potassium carbonate 3.6kg, 8-bromo-7-(2-butyne)-3-methylxanthine 2.8kg, 2-chloromethyl-4 -Methyl-quinazoline 3.2kg, potassium iodide 0.66kg, stir, heat up to 44°C and stir for 3hr, detect 8-bromo-7-(2-butyne)-3-methylxanthine raw material residues are not more than 1.0% Stop, cool down to below 40°C, add 42kg of purified water dropwise at a constant speed under stirring, continue to cool down and cool to 15°C, keep stirring for 2 hours, centrifuge, and rinse the solid with 13kg of purified water to obtain a khaki-yellow wet product, put it in a double-cone dryer Dry at 50°C under reduced pressure (-0.09Mpa) for about 18hr until the weight loss on drying does not exceed 1.0%, and 4.35kg of intermediate I is obtained as a khaki-yellow dry product.

[0029] 2. Preparation of intermediate II:

[0030] Add 40kg of dipolar aprotic organic solvent N,N-dimethylfo...

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

An industrial production method of linagliptin. According to the molar ratio, 8-bromo-7-(2-butyne)-3-methylxanthine and 2-chloromethyl-4-methylquinazoline are added to the dipolar aprotic organic solvent, and then the base is added and potassium iodide, crystallized, filtered and dried to obtain intermediate I; according to the molar ratio, intermediate I and (R)-3-tert-butoxycarbonylaminopiperidine were added to the dipolar aprotic organic solvent, and alkali was added to analyze crystallized, filtered and washed to remove inorganic salts, and the solvent was removed under reduced pressure to obtain the crude product, which was then crystallized from methanol and isopropanol to obtain intermediate II; according to the volume ratio, intermediate II and the deprotection reagent were added to the reaction solvent, and crystallized to obtain The crude product was recrystallized with ethanol, filtered and dried to obtain the final product of linagliptin. The method of the invention can greatly shorten the production cycle, save production cost, obtain intermediates with higher purity, and better effect of removing impurities. The method is safe, reliable, simple and easy to operate, and has good repeatability.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to an industrial production method of linagliptin. Background technique [0002] Linagliptin Tablets, Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, can improve type 2 diabetes mellitus (T2DM) adult patients on the basis of diet control and physical exercise levels of blood sugar control. However, the current industrial preparation method has low intermediate purity, complicated operation, high cost and great environmental pollution. Contents of the invention [0003] The technical problem to be solved by the present invention is to overcome the defects of the prior art and provide an industrial production method of linagliptin. [0004] In order to solve the above technical problems, the present invention provides the following technical solutions: a method for industrial production of linagliptin, the solution of which is as follows: [0005] 1. Add 8-br...

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): C07D473/04
CPCC07D473/04
Inventor 王步通蒋维胡孟奇
Owner 合肥远志医药科技开发有限公司
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