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

One-pot synthetic method for N-t-butyl-aminocarbonyl-3-methyl-L-valine

A technology of tert-butylaminocarbonyl and synthetic method, which is applied in the field of drug synthesis, can solve the problems of affecting the yield of final product, greatly affecting the pH, and long synthesis time, and achieves shortened reaction cycle, controllable conditions, and low production cost Effect

Inactive Publication Date: 2013-11-20
SUZHOU UUGENE BIOPHARMA
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this synthetic method is relatively simple, the pH has a greater impact on the reaction. For example, when the pH of the system is 10.3, the product yield is 87%, and when the pH of the system is 10.2, the product yield is 91%, and the obtained product yield is higher. , it is necessary to control the pH value more strictly, the operation is more difficult, and it takes 6 hours to react after adding materials, and the synthesis time is longer
In addition, because tert-butyl isocyanate is used in this synthetic method, two by-products of dipeptide polymer and urea are also easily produced in the reaction, which affects the yield of the final product.

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
  • One-pot synthetic method for N-t-butyl-aminocarbonyl-3-methyl-L-valine
  • One-pot synthetic method for N-t-butyl-aminocarbonyl-3-methyl-L-valine
  • One-pot synthetic method for N-t-butyl-aminocarbonyl-3-methyl-L-valine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] In a 500mL reaction flask, dissolve 36.5g of tert-butylamine in 150mL of dichloromethane to form a reaction solution, cool the reaction solution to 0°C, first add 81g of N,N'-carbonyldiimidazole, and react for 30 minutes under stirring until the reaction is complete as detected by TLC; Then add 65.5gL-leucine to the reaction solution, and react for 30min under stirring until the reaction is complete as detected by TLC; then add the reaction solution to ice water, extract with 150mL dichloromethane, and concentrate under reduced pressure at 35°C to obtain White solid; get 200g of the gained white solid and use n-heptane to make a slurry, vacuum-dry after suction filtration to obtain 113g of the final product N-tert-butylaminocarbonyl-3-methyl-L-valine, the purity is 99.6%, and the yield is 98 %.

Embodiment 2

[0038] In a 100mL reaction flask, 73g of tert-butylamine was dissolved in 300mL of tetrahydrofuran to form a reaction solution. When the reaction solution was cooled to 5°C, 162g of N,N'-carbonyldiimidazole was added and stirred for 40 minutes until the reaction was detected by TLC; then 131g of L-leucine The acid was added to the reaction solution, stirred for 40 min until the reaction was detected by TLC, then the reaction solution was added to ice water, extracted with 300 mL of tetrahydrofuran, and concentrated under reduced pressure at 40°C to obtain a white solid; the obtained white solid was beaten with methanol, After suction filtration and vacuum drying, 225 g of the final product N-tert-butylaminocarbonyl-3-methyl-L-valine was obtained, with a purity of 99.5% and a yield of 97.6%.

Embodiment 3

[0040] In a 250mL reaction flask, 18g of tert-butylamine was dissolved in 70mL of methanol to form a reaction solution. When the reaction solution was cooled to -5°C, 40g of N,N'-carbonyldiimidazole was added and stirred for 20 minutes until the reaction was detected by TLC; Amino acid was added to the reaction solution, stirred for 20 minutes until the reaction was detected by TLC, then the reaction solution was added to ice water, extracted with 70mL n-butanol, and concentrated under reduced pressure at 30°C to obtain a white solid; the obtained white solid was used in Slurry with ether, vacuum-dry after suction filtration to obtain 55.2 g of the final product N-tert-butylaminocarbonyl-3-methyl-L-valine, with a purity of 99.2% and a yield of 97.5%.

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 one-pot synthetic method for the intermediate of boceprevir, i.e., N-t-butyl-aminocarbonyl-3-methyl-L-valine, which belongs to the technical field of drug synthesis. The synthetic method comprises the following steps: dissolving tert-butylamine in a solvent to form a reaction solution, cooling the reaction solution to a temperature of -5 to 5 DEG C, adding N,N'-carbonyldiimidazole into the reaction solution and carrying out a reaction with stirring for 20 to 40 min until a compound represented by formula (I) is obtained after completion of the reaction; and then adding L-leucine into the reaction solution, carrying out a reaction with stirring for 20 to 40 min until the reaction is finished, adding the totally reacted reaction solution into ice water and carrying out extraction, pressure reduced concentration, pulping, pumping filtration and vacuum drying so as to obtain N-t-butyl-aminocarbonyl-3-methyl-L-valine. The synthetic method has the advantages of cheap and easily available raw materials, greenness, environment friendliness, simple reaction conditions, a high conversion rate, a few generated by-products and high yield and purity of the product, N-t-butyl-aminocarbonyl-3-methyl-L-valine.

Description

technical field [0001] The invention relates to a method for synthesizing a boceprevir intermediate, in particular to a one-pot method for synthesizing boceprevir intermediate N-tert-butylaminocarbonyl-3-methyl-L-valine, which belongs to drug synthesis technology field. Background technique [0002] Hepatitis C protease inhibitor Boceprevir (Boceprevir), its Chinese name: (1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutane-2 -yl)-3-[(2S)-2-(tert-butylcarbamoylamino)-3,3-dimethylbutyryl]-6,6-dimethyl-3-azabicyclo[3.1. 0] Hexane-2-carboxamide; English chemical name: (1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-[(2S) -2-(tert-butylcarbamoylamino)-3,3-dimethylbutanonyl]-6,6-dimethyl-3-azabicylo[3.1.0]hexane-2-carboxamide; Molecular formula: C 27 h 45 N 5 o 5 ; Molecular Weight: 519.68; CAS Registry Number: 394730-60-0. Its structural formula is as follows: [0003] [0004] Boceprevir (SCH-503034) was developed by Schering-Ploug (Schering-Ploug) in the Uni...

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): C07C275/16C07C273/02
Inventor 肖坤福江锋王伸勇王晓俊胡隽恺
Owner SUZHOU UUGENE BIOPHARMA
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