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

A kind of acid salt of imidazole acetonitrile derivative and its preparation method and application

A technology of imidazole acetonitrile and derivatives, applied in organic chemistry, antifungal agents, etc., can solve the problems of great influence on the physical and chemical properties of drugs, low yield, high content of isomer impurities, etc., to achieve dissolution and drug stability , high yield, good water solubility

Active Publication Date: 2019-05-10
浙江东亚药业股份有限公司
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it does not disclose what kind of salt its pharmaceutically acceptable salt is, and even does not disclose the scope of its pharmaceutically acceptable salt. However, in the art, the different forms of salts formed by different drugs have a greater impact on the physical and chemical properties of the drug. , there are too many uncertainties, and there are no other reports on the specific preparation of luliconazole salt compounds
Therefore, the inventor hopes to develop one or a class of practical luliconazole salts through research; Low problem, the inventor also hopes to obtain the corresponding intermediate raw materials through the research on the preparation process of the drug and its salt, so as to achieve the effect of easier purification and high 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
  • A kind of acid salt of imidazole acetonitrile derivative and its preparation method and application
  • A kind of acid salt of imidazole acetonitrile derivative and its preparation method and application
  • A kind of acid salt of imidazole acetonitrile derivative and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] A kind of imidazole acetonitrile derivative hydrobromide, the structural formula of this imidazole acetonitrile derivative hydrobromide is shown in following formula (I-1):

[0034]

[0035] The specific preparation method of imidazole acetonitrile derivative hydrobromide (formula (I-1)) in the present embodiment is as follows:

[0036] Weigh the compound of formula Ⅱ (Z / E)-(4R)-4-(2,4-dichlorophenyl)-1,3-dithiolane-2-substitution (1H-imidazole-1-substitution) 1 mol of acetonitrile was dissolved in ethyl acetate solvent, and then 1.3 mol of corresponding HBr was added. Then, the temperature of the reaction system was controlled at 60°C for 2.5 hours. Fully analyze the corresponding solid product, filter and dry to obtain the corresponding solid intermediate product formula I-1 compound (E)-(4R)-4-(2,4-dichlorophenyl)-1,3-dithiopentane Cyclo-2-substituted (1H-imidazole-1-substituted) acetonitrile hydrobromide, the molar yield is 90%, and the purity reaches 99.7%.

...

Embodiment 2

[0042] A kind of imidazole acetonitrile derivative hydrochloride, the structural formula of this imidazole acetonitrile derivative hydrochloride is shown in following formula (I-2):

[0043]

[0044] The specific preparation method of the imidazole acetonitrile derivative hydrochloride (formula (I-2)) in the present embodiment is as follows:

[0045] Weigh 1 mol of compound (E)-4-(2,4-dichlorophenyl)-1,3-dithiolane-2-substituted (1H-imidazole-1-substituted) acetonitrile in ethyl acetate In the ester solvent, then pass through dry HCl gas, stop when there are many solids, filter, and dry to obtain the corresponding solid intermediate product formula Ⅰ-1 compound (E)-4-(2,4-dichlorophenyl)-1 , 3-dithiolane-2-subsubstituted (1H-imidazole-1-substituted) acetonitrile hydrochloride, the molar yield was 91%, and the purity reached 99.8%.

[0046] Melting point Mp: 214.5-217.1°C.

[0047] MS(m / z): 354[M+H] + .

[0048] 1 H-NMR (400MHz, DMSO-d 6 ):4.13~4.25(m,2H),5.88(t,J=4.0H...

Embodiment 3

[0050] A kind of imidazole acetonitrile derivative fumarate, the structural formula of this imidazole acetonitrile derivative fumarate is shown in following formula (I-3):

[0051]

[0052] The specific preparation method of imidazole acetonitrile derivative fumarate (formula (I-3)) in the present embodiment is as follows:

[0053] Weigh 1mol of compound (E)-(4S)-4-(2,4-dichlorophenyl)-1,3-dithiolane-2-substituted (1H-imidazole-1-substituted) acetonitrile Dissolve in toluene solvent, then add 0.8mol of the corresponding fumaric acid, then, control the temperature of the reaction system to react at 90°C for 1.5 hours, after the reaction, continue to stir and cool down to normal temperature to fully analyze the corresponding fumaric acid. The solid product was filtered and dried to obtain the corresponding solid intermediate product formula Ⅰ-3 compound (E)-(4S)-4-(2,4-dichlorophenyl)-1,3-dithiolane-2 -subsubstituted (1H-imidazole-1-substituted) acetonitrile fumarate, the mo...

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 an imidazole acetonitrile derivative acid salt as well as a preparation method and an application thereof, belongs to the technical field of drug synthesis, and aims to solve the problem about how to improve stability and increase the yield. The method comprises steps as follows: an imidazole acetonitrile derivative is dissolved in a water-insoluble polar organic solvent, then corresponding acid is added for a salt forming reaction, and the acid salt of the product imidazole acetonitrile derivative is gradually separated out, and applied to preparation of Luliconazole. The acid salt itself has better stability and used as an intermediate for preparing Luliconazole at the same time, the problem of mutual inversion of Z-E configuration in the Luliconazole preparation process can be solved, the Z configuration can be inverted into the E configuration, the configuration inversion stability is guaranteed, and the yield is higher. The effects of simple technology and easiness in operation are also realized.

Description

technical field [0001] The invention relates to an acid salt of an imidazole acetonitrile derivative and a preparation method and application thereof, belonging to the technical field of drug synthesis. Background technique [0002] Luliconazole is an imidazole antifungal drug developed by Nippon Pesticide Co., Ltd., which was approved in June 2005. rotten, vitiligo), etc. Compared with the previous antifungal topical drugs, its biggest advantage is high skin retention rate, short drug cycle, good curative effect and not easy to relapse, so it has greater competitiveness. The structural formula of luliconazole is shown below: [0003] [0004] The chemical name of luliconazole is (E)-(4R)-4-(2,4-dichlorophenyl)-1,3-dithiolane-2-substituted (1H-imidazole-1-substituted)acetonitrile . [0005] Most of the existing literature is about the preparation method of luliconazole and the research on the crystal form of the compound. Specifically, different crystal forms of the ...

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 Patents(China)
IPC IPC(8): C07D409/06A61P31/10
CPCC07D409/06
Inventor 王海平池骋罗建国童云利何建鹏高扬
Owner 浙江东亚药业股份有限公司