Spirocyclic degronimers for target protein degradation
A technology targeting ligands and carbocycles, applied in the fields of resisting vector-borne diseases, medical preparations with inactive ingredients, and medical preparations containing active ingredients, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Examples
Example Embodiment
[0833] Representative example 1: 2,6-diazaspiro[3.5]nonane-5,7-dione
[0834]
[0835] 3-(3-Methoxy-3-oxopropyl)azetidine-1,3-dicarboxylic acid 1-(tert-butyl)3-methyl ester:
[0836]
[0837] Azetidine-1,3-dicarboxylic acid 1-(tert-butyl)3-methyl ester (1 equivalent) was dissolved in dry tetrahydrofuran and cooled to -78°C. Then a solution of lithium hexamethyldisilazide (1.0 M in tetrahydrofuran) (1.1 equivalents) was added dropwise and the solution was stirred for 1 hour. Then methyl 3-bromopropionate (1 equivalent) was added dropwise. The reaction was allowed to stir for 30 minutes and then gradually warmed to room temperature. When the reaction was judged to be complete based on TLC or LCMS analysis, it was quenched with saturated aqueous ammonium chloride solution and diluted with ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3x). The combined organic layer was washed with brine and dried over sodium sulfate, and then c
Example Embodiment
[0860] Representative example 2: 2-((2-hydroxyethyl)sulfonyl)-2,6-diazaspiro[3.5]nonane-5,7-dione
[0861]
[0862] 1-(Vinylsulfonyl)azetidine-3-carboxylic acid methyl ester:
[0863]
[0864] The Boc protected azetidine is dissolved in dioxane. HCl (4N in dioxane) was added and the solution was stirred at room temperature for 12 hours. Then the solvent was evaporated under reduced pressure. Then azetidine (1 equivalent) was dissolved in DCM and cooled to -40°C. Add triethylamine (1.5 equivalents), then DMAP (0.1 equivalents). A solution of vinylsulfonyl chloride (1.2 equivalents) in DCM was slowly added dropwise. The mixture was stirred until the starting material was consumed as judged by TLC or LCMS analysis. The reaction was then warmed to room temperature and filtered through silica gel. The filtrate was concentrated under reduced pressure and the crude material was purified on silica gel.
[0865] 1-((2-((tert-butyldimethylsilyl)oxy)ethyl)sulfonyl)azetidine-3-carboxylic aci
Example Embodiment
[0876] Representative example 3: 2-(2-hydroxyethyl)-2-methyl-1-oxa-6-azaspiro[3.5]nonane-5,7-dione:
[0877]
[0878] To a solution of 4-butenoic acid (1 equivalent) in dichloromethane at 0°C was added trimethylamine (2 equivalents), isobutyl chloroformate (1.1 equivalents) and N,O-dimethylhydroxylamine (1.05 Equivalent), then trimethylamine (2 equivalents). The reaction was stirred overnight at room temperature. Then it was treated with saturated aqueous sodium bicarbonate solution. The organic layer was separated and the aqueous layer was extracted with dichloromethane (3x). The combined organic layer was washed with brine and dried over sodium sulfate, then concentrated. The crude material was purified on silica gel (Goncalves-Martin, M. et al., Synlett, 2009, 17, ). The Weinreb amide was then dissolved in dry tetrahydrofuran and cooled to 0°C. Then vinyl Grignard reagent (0.7M in THF, 1.2 equivalents) was added dropwise. After 1 hour, the reaction was quenched with satura
PUM
![No PUM](https://release-static-eureka.zhihuiya.com/ssr/23.2.0/_nuxt/noPUMSmall.5c5f49c7.png)
Abstract
Description
Claims
Application Information
![application no application](https://release-static-eureka.zhihuiya.com/ssr/23.2.0/_nuxt/application.06fe782c.png)
- R&D Engineer
- R&D Manager
- IP Professional
- Industry Leading Data Capabilities
- Powerful AI technology
- Patent DNA Extraction
Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.
© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap