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

Preparation method of 1,4-dioazo-cycloheptane derivative

A technology for diazepane and derivatives is applied in the field of drug synthesis, which can solve the problems of poor stability, low total yield, and affect reproducibility, and achieves the effects of mild reaction conditions, short synthetic route, and optimized operation.

Inactive Publication Date: 2016-08-31
WUCHANG UNIV OF TECH +1
View PDF2 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] This method is on the fluoroisoquinoline ring in series step by step, and the steps in series are longer, resulting in lower total yield
And when preparing 1,4-diazepane ring, sodium hydroxide is used in dimethyl sulfoxide, which is not easy to operate
In addition, this method requires the synthesis of unstable intermediates during the synthesis process, and unstable intermediates are easily converted to other compounds and have poor stability, thus affecting the reproducibility of the method
It can be seen that this method has obvious shortcomings and limitations

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
  • Preparation method of 1,4-dioazo-cycloheptane derivative
  • Preparation method of 1,4-dioazo-cycloheptane derivative
  • Preparation method of 1,4-dioazo-cycloheptane derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] A preparation method of (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-diazepane, the steps of which are:

[0039] 1) 2-(S)-1-(4-fluoroisoquinoline-5-sulfinylamino)-N-(tert-butoxycarbonyl)-N-(3-tert-butyldimethylsilyloxy The preparation of propyl) propylamine:

[0040] Dissolve 2.3g (6.72mmol) of 2-(S)-2-amino-N-(tert-butoxycarbonyl)-N-(3-tert-butyldimethylsilyloxypropyl)propylamine in 15ml of dichloromethane After cooling down to -5-0°C, add 0.74g (7.33mmol) triethylamine and 0.15g 4-dimethylaminopyridine, slowly add 1.5g (6.1mmol) 4-fluoroisoquinoline-5 under stirring - Sulfonyl chloride, react at -5-0°C for 45min, then rise to 20-30°C, react at 20-30°C for 16h, after the reaction is completed, add 10mL of water to the resulting system after the reaction, and extract with 8ml of dichloromethane 3 times, after the extraction was completed, the resulting organic phase was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated an...

Embodiment 2

[0074] A preparation method of (S)-(-)-1-(4-bromoisoquinolin-5-yl)sulfonyl-2-methyl-1,4-diazepane, the steps of which are:

[0075] 1) 2-(S)-1-(4-bromoisoquinoline-5-sulfinylamino)-N-(tert-butoxycarbonyl)-N-(3-tert-butyldimethylsilyloxy The preparation of propyl) propylamine:

[0076] Dissolve 1.87g (5.38mmol) of 2-(S)-2-amino-N-(tert-butoxycarbonyl)-N-(3-tert-butyldimethylsilyloxypropyl)propylamine in 5ml of dichloromethane After cooling down to -5-0°C, 1.73g (17.13mmol) of triethylamine was added thereto, and 1.5g (4.89mmol) of 4-bromoisoquinoline-5-sulfonyl chloride was slowly added under stirring. After reacting at ℃ for 45min, rise to 20-30℃, and react at 20-30℃ for 16h. After the reaction is completed, add 8mL of water to the system obtained after the reaction, and extract 3 times with 6-8ml of dichloromethane. After the extraction is completed, , the resulting organic phase was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated and dri...

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 preparation method of a 1,4-dioazo-cycloheptane derivative. The preparation method comprises the steps of carrying out multiple coupling on a compound of a formula (VI) and a compound of a formula (V) at -5-0 DEG C in aromatic hydrocarbon or a halogenated hydrocarbon solvent in the presence of alkali, after the coupling, removing hydroxyl protection from the compound of the formula (VI) by virtue of TBAF, carrying out self-cyclization by virtue of a Mitsunobu reaction to obtain a compound of a formula (II), and removing amino protection from the compound of the formula (II) by virtue of a hydrochloric acid ethyl acetate solution, so as to obtain the target compound 1,4-dioazo-cycloheptane derivative. The preparation method has the advantages that synthetic steps are few, the reaction condition of each step is mild, and the operation is simple convenient, so that the production cost is lowered; and more importantly, the yield of the 1,4-dioazo-cycloheptane derivative synthesized by the method is high.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a method for preparing a 1,4-diazepane derivative. The 1,4-diazepane derivative is used as a medicine and is suitable for cerebral infarction, cerebral hemorrhage, The prevention and treatment of cerebrovascular disorders such as subarachnoid hemorrhage and cerebral edema can be particularly used as a therapeutic agent for glaucoma. Background technique [0002] The known (s)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-diazepane is the following formula (I) [0003] [0004] The compounds shown, especially their hydrochloride-dihydrates are water-soluble crystals, are non-hygroscopic, and have excellent chemical stability, so they can be used as pharmaceuticals. These isoquinoline-5-sulfonamide compounds are known to be useful in the prevention and treatment of cerebrovascular disorders such as cerebral infarction, cerebral infarction, cerebral hemorrhage, su...

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): C07D401/12
CPCC07D401/12
Inventor 王小华张留丁冠军黄楚华
Owner WUCHANG UNIV OF TECH
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