Unlock instant, AI-driven research and patent intelligence for your innovation.

Diverse arylimidazole quaternary ammonium salt, preparation method and application thereof

A technology of diversity and imidazoles, which is applied in the field of diverse aryl imidazole quaternary ammonium salts and their preparation and application, can solve the problems of limited industrial application prospects, failure to obtain target products, and low yield of arylaminoboronic acid Waiting for a question

Inactive Publication Date: 2014-01-01
SHANGHAI SAIIA CHEM PROD
View PDF12 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ellman successfully developed an asymmetric synthesis method induced by chiral tert-butylsulfinamide, see literature Melissa A.Beenen, Chihui An, and Jonathan A.Ellman, J.Am.Chem.Soc.2008,130,6910 -6911 report, the method utilizes pinacol diborane ester to react with chiral tert-butylsulfinimide under the catalysis of (ICy)CuOtBu / sodium tert-butoxide to obtain chiral α-aminoboronic acid derivatives, Although it has the advantages of high stereoselectivity and high yield of aliphatic chain alkyl substituted imine substrates, there are still two problems in this method at present, 1) it uses the tert-butoxide copper of NHC Copper carbene complexes are used as catalysts, which can only be prepared and stored in specific places (such as glove boxes), which limits its industrial application prospects; 2) Ellman’s method has limitations in the type of substrate, usually The yield of alkylaminoboronic acid is good (yield: 74-88%), but the test found that the yield of arylaminoboronic acid is not good (yield: 52-61%), and even the target product cannot be obtained;

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
  • Diverse arylimidazole quaternary ammonium salt, preparation method and application thereof
  • Diverse arylimidazole quaternary ammonium salt, preparation method and application thereof
  • Diverse arylimidazole quaternary ammonium salt, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Synthesis of compound L-01':

[0081] Step 1: Synthesis of Compound L-01:

[0082]

[0083] O-phenylenediamine (2.162g, 20mmol), bromobenzene (6.281g, 40mmol), Pd 2 (dba) 3 (0.916g, 1mmol) (the Pd content of the reagent is 21.5%), BINAP (0.934g, 7.5%eq), sodium tert-butoxide (5.766g, 3eq) and anhydrous toluene (20ml) were added to the reaction tube protected by nitrogen , temperature 110°C. React overnight. After the reaction, filter paper was used to remove the solids, and the solids were washed with ethyl acetate. The obtained liquids were combined, spin-dried, and passed through the column to obtain the product as off-white solid 4.478g, with a yield of 86%.

[0084] 1 H-NMR (CDCl 3 ,δ,ppm):7.33-7.29(m,6H),7.01-6.91(m,8H),5.65(s,2H,NH). 13 C-NMR (CDCl 3 , δ, ppm): 145.0, 135.0, 129.4, 122.5, 120.4, 119.5, 116.7.

[0085] Step 2: Synthesis of compound L-01':

[0086]

[0087] Add 2.11 g (8 mmol) of the product from the previous step into 16 ml of trime...

Embodiment 2

[0090] Synthesis of compound L-02':

[0091] Step 1: Synthesis of Compound L-02:

[0092]

[0093]o-Phenylenediamine (2.162g, 20mmol), p-bromotoluene (6.805g, 40mmol), Pd 2 (dba) 3 (0.916g, 1mmol) (the Pd content of the reagent is 21.5%), BINAP (0.934g, 7.5%eq), sodium tert-butoxide (5.766g, 3eq) and anhydrous toluene (20ml) were added to the reaction tube protected by nitrogen , temperature 110°C. React overnight. After the reaction, filter paper was used to remove the solid, and the solid was washed with ethyl acetate. The obtained liquid was combined, spin-dried, and passed through the column to obtain the product as gray solid 4.614g, with a yield of 80%.

[0094] 1 H-NMR (CDCl 3 ,δ,ppm):7.33-7.29(m,6H),7.01-6.91(m,8H),5.65(s,2H,NH). 13 C-NMR (CDCl 3 , δ, ppm): 145.0, 135.0, 129.4, 122.5, 120.4, 119.5, 116.7.

[0095] Step 2: Synthesis of compound L-02':

[0096]

[0097] Add 2.31g (8mmol) into 16ml of trimethyl orthoformate, add dropwise 0.8ml of 36% hydro...

Embodiment 3

[0100] Synthesis of compound L-03':

[0101] Step 1: Synthesis of Compound L-03:

[0102]

[0103] O-phenylenediamine (1eq), bromide (1eq), Pd2(dba)3 (5%eq) (the Pd content of the reagent is 21.5%), BINAP (7.5%eq), sodium tert-butoxide (3eq) and none Water toluene (1ml / mmol, for bromide) was added to the reaction tube protected by nitrogen, and the temperature was 110°C. React overnight. After the reaction, filter paper was used to remove the solid, and the solid was washed with ethyl acetate, and the obtained liquid was combined, spin-dried, and passed through the column to obtain the product. Yield 86%

[0104] Step 2: Synthesis of compound L-03':

[0105]

[0106] Add the product from the previous step (2mmol) into 4ml (2ml / mmol) of trimethyl orthoformate, add dropwise 0.2ml (0.1ml / mmol) of concentrated hydrochloric acid, and 1drop of formic acid. Heated to 80 degrees, reacted for 2 hours. TLC followed disappearance of starting material. The reaction solution w...

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 present invention discloses a diverse arylimidazole quaternary ammonium salt, a preparation method and an application thereof. The diverse arylimidazole quaternary ammonium salt is a compound represented by a formula (L-n'). The diverse arylimidazole quaternary ammonium salt has the following beneficial effects that: the diverse arylimidazole quaternary ammonium salt can be prepared through the one-pot method and is not prepared in a glove box, the raw material (aliphatic or aromatic imine) is subjected to the reaction, the yield is 78-94%, and the target product with high optical purity dr of more than 98:2 is obtained. According to the present invention, operations can be simplified, the yield can be increased, importantly an application range of the compound is expanded, and wide versatility is provided.

Description

technical field [0001] The invention relates to an aryl imidazole quaternary ammonium salt, a preparation method and application thereof. Background technique [0002] In recent years, α-aminoboronic acid, as the key pharmacophore of serinase antagonism, has attracted more and more attention in drug design. Due to the unique physicochemical properties and spatial structure of boron atoms (with empty p orbitals and small atomic radius), α-aminoboronic acids can be designed as various hydrolase inhibitors with important roles. For example, the literature Shenvi, al., US4499082 (1985) Shenvi, etc. revealed that peptidylaminoboronic acid TM-1 compounds can be used as inhibitors of proteolytic enzymes, the literature Kentter, Shenvi, al., US5187157 (1993), US5242904 (1993), US5250720 (1993) Kentter, Shenvi revealed that peptidylaminoboronic acid TM-1 compounds can also be used as reversible inhibitors of insulin-like serine hydrolase, which can act on thrombin, plasma kallikrein...

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): C07D235/10C07D235/12C07D235/24C07D235/02C07D401/04C07D471/04C07D487/04
CPCB01J31/183B01J31/1835B01J31/2217B01J31/2273B01J2231/344B01J2531/0238B01J2531/0261B01J2531/16C07D235/08C07D401/14C07D471/04C07D487/04C07F5/025
Inventor 孙智华范尔康
Owner SHANGHAI SAIIA CHEM PROD