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

Method for selective deuteration of aromatic ring benzyl carbon-hydrogen bonds

An aromatic ring benzylic position and selective technology, applied in the field of hydrogen-deuterium exchange, can solve the problems of poor deuterium substitution selectivity and narrow substrate applicability, and achieve the effects of simple operation, convenient operation and handling, and wide compatibility

Active Publication Date: 2021-10-29
WESTLAKE UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Aiming at the shortcomings of the existing narrow substrate applicability and poor deuteration selectivity, the present invention provides a method for selective deuteration of the carbon-hydrogen bond at the benzylic position of the aromatic ring

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
  • Method for selective deuteration of aromatic ring benzyl carbon-hydrogen bonds
  • Method for selective deuteration of aromatic ring benzyl carbon-hydrogen bonds
  • Method for selective deuteration of aromatic ring benzyl carbon-hydrogen bonds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035]

[0036] In a nitrogen atmosphere, sequentially add raw material 1 (0.2mmol, 30.0mg), catalyst 10 (0.005mmol, 3.5mg), AgNTf 2 (0.02mmol, 7.8mg), Li 3 PO 4 (0.02mmol, 2.3mg), finally add acetone-d 6 (0.2 mL). After the reaction was stirred at 120°C for 24 hours, it was cooled to room temperature, and the internal standard 1,1,2,2-tetrachloroethane (0.2mmol, 33.6mg) and deuterated chloroform (0.5mL) were added, and determined by H NMR spectroscopy. The benzylic deuterated rate of the target product was 86%, and the NMR yield was 99%. 1 H NMR (500MHz, Chloroform-d) δ7.16(d, J=8.7Hz, 2H), 6.85(d, J=8.7Hz, 2H), 3.80(s, 3H), 2.92–2.80(m, 0.14H ,86%D), 1.28–1.16(m,6H). 13 C NMR(126MHz,Chloroform-d)δ157.6,127.2,141.0,113.7,55.2,33.2(benzylic carbon of remaining1),32.8(t,J=19.5Hz,benzylic carbon of deuterated 1),24.19–24.08(m,– CH 3 carbon).

Embodiment 2

[0038]

[0039] In a nitrogen atmosphere, sequentially add raw material 2 (0.2mmol, 24.0mg), catalyst 1 (0.005mmol, 3.1mg), AgOTf (0.02mmol, 5.1mg), NaOTf (0.2mmol, 34.4mg), and finally add methanol-d 4 (0.2 mL). After the reaction was stirred at 120°C for 24 hours, it was cooled to room temperature, and the internal standard 1,1,2,2-tetrachloroethane (0.2mmol, 33.6mg) and deuterated chloroform (0.5mL) were added, and determined by H NMR spectroscopy. The benzylic deuterated rate of the target product was 50%, and the NMR yield was 99%. 1 H NMR (500MHz, Chloroform-d) δ7.30–7.26(m,2H),7.23–7.21(m,2H),7.19–7.15(m,1H),2.95–2.86(m,0.50H,50%D ),1.26–1.21(m,6H). 13 C NMR(126MHz,Chloroform-d)δ148.74–148.71(m,aromatic carbon adjacent to benzylic carbon),128.2,126.3,125.6,34.0(benzylic carbon of remaining 2),33.53(t,J=19.5Hz,benzylic carbon of deuterated 2),23.81–23.70(m,–CH 3 carbon).

Embodiment 3

[0041]

[0042] In a nitrogen atmosphere, sequentially add raw material 3 (0.2mmol, 29.7mg), catalyst 11 (0.005mmol, 3.7mg), AgNTf 2 (0.02mmol, 7.8mg), NaNTf 2 (0.2mmol, 60.6mg), finally add methanol-d 4 (0.2 mL). After the reaction was stirred at 120°C for 24 hours, it was cooled to room temperature, and the internal standard 1,1,2,2-tetrachloroethane (0.2mmol, 33.6mg) and deuterated chloroform (0.5mL) were added, and determined by H NMR spectroscopy. The benzylic deuterated rate of the target product was 83%, and the NMR yield was 99%. 1 H NMR (500MHz, Chloroform-d) δ7.31 (d, J = 8.3Hz, 2H), 7.14 (d, J = 8.3Hz, 2H), 2.38–2.31 (m, 0.51H, 83%D), 1.34 (s,6H). 13 C NMR(126MHz,Chloroform-d)δ148.2,134.8–134.7(m,aromatic carbon adjacent to benzylic methyl carbon),128.7,125.1,34.3,31.4,20.8–19.4(m,benzylic methyl carbon).

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 method for selective deuteration of aromatic ring benzyl carbon-hydrogen bonds. According to the method, a metal rhodium catalyst is used for performing eta6 coordination activation on an aromatic ring, so that hydrogen-deuterium exchange can be selectively performed on the aromatic ring and a deuterated reagent at a benzyl position; strong acid or strong alkali does not need to be added, the cheap and easily available deuterated reagent is adopted as a deuterium source, so that the method has good universality for various aromatic hydrocarbons with different functional groups, can be applied to later selective deuteration of complex drug molecules, and has high application value.

Description

technical field [0001] The invention relates to the technical field of hydrogen-deuterium exchange, in particular to a method for selective deuteration of benzylic carbon-hydrogen bonds starting from ordinary aromatic hydrocarbons. Background technique [0002] Due to the kinetic isotope effect of deuterium atoms, C–D bonds are more stable than C–H bonds in organisms. In drug development, the introduction of deuterium atoms to specific positions of target molecules, such as the benzylic position of aryl groups, can significantly change its pharmacokinetic properties (ADME). In addition, deuterated compounds are also widely used in the study of reaction mechanism. [0003] At present, there are mainly the following types of methods for the synthesis of compounds deuterated by benzylic carbon-hydrogen bonds: [0004] (1) Starting from commercially available deuterated raw materials, it is obtained through multi-step synthesis. This method is usually cumbersome and the overa...

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): C07B59/00C07C5/00C07C15/085C07C15/02C07C15/16C07C15/14C07C13/28C07C13/465C07C13/48C07C13/567C07C13/60C07C17/35C07C22/08C07C25/18C07C25/22C07C41/18C07C43/164C07C43/205C07C51/347C07C57/30C07C67/30C07C69/734C07C69/612C07C209/68C07C211/27C07C211/48C07C231/12C07C233/11C07C233/05C07C233/18C07C303/40C07C311/16C07D207/267C07D209/08C07D209/48C07D309/10C07D311/04C07D311/82C07F9/32C07J1/00
CPCC07B59/001C07B59/002C07B59/007C07D309/10C07J1/0011C07C231/12C07C41/18C07C5/00C07D311/82C07D311/04C07C209/68C07C17/35C07C67/30C07F9/3288C07D207/267C07C303/40C07D209/48C07D209/08C07C51/347C07B2200/05C07C2603/26C07C2602/10C07C2603/18C07C2602/08C07C2601/14C07C233/05C07C233/18C07C43/205C07C15/085C07C15/02C07C15/16C07C15/14C07C13/28C07C13/465C07C13/48C07C13/567C07C13/60C07C211/48C07C25/18C07C25/22C07C43/164C07C69/612C07C69/734C07C233/11C07C311/16C07C211/27C07C22/08C07C57/30Y02P20/52
Inventor 石航康麒凯李运通
Owner WESTLAKE UNIV
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