用有机试剂为图书馆合成的异芳乙烯的自动化
Javier Mazuela1, Aritz Martinez1, Paula Cervantes-Cerrada1
1Global Discovery Chemistry, Chemical Capabilities, Analytical, and Purification, Janssen Research and Development, Janssen-Cilag, S.A., C/Jarama 75, Toledo 45007, Spain.
本研究引入了一种自动化流体化学工作流程,用于使用有机试剂快速多样化异二甲基乙烯. 这种方法加速了在药物化学中发现新的生物活性化合物的过程.
科学领域:
- 合成有机化学 合成有机化学
- 药用化学 医学化学
- 流动化学 流动化学
背景情况:
- Heteroaryl thioethers 是药物化学中至关重要的支架.
- 这些化合物的高效功能化对于药物发现至关重要.
- 目前用于修改 thioether 的现有方法可能耗时且产量低.
研究的目的:
- 开发一个自动化的高吞吐量工作流程,用于功能化 heteroaryl thioethers.
- 为了使药物化学图书馆的快速多样化.
- 为了提高在异芳乙烯中修改C ((sp3) 中心的速度和效率.
主要方法:
- 实现一个自动化流体化学平台.
- 使用各种基有机试剂进行合反应.
- 采用了各种乙基板来测试广泛的适用性.
主要成果:
- 通过各种有机试剂成功地实现了对异甲基乙烯的功能化.
- 在不同的基质和试剂中证明了该平台的广泛适用性.
- 实现了具有C(sp3) 中心的异芳乙烯的高效修饰.
结论:
- 开发的自动化流程工作流程对于 thioether 功能化非常高效.
- 这个平台促进了药物发现的图书馆快速多样化.
- 它是加速药物化学项目的一个宝贵资源.
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相关概念视频
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Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
Preparation of Alkynes: Dehydrohalogenation
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
Electrophilic Addition to Alkynes: Hydrohalogenation
Electrophilic Addition to Alkynes: Halogenation
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a Ï bond. In alkynes, the presence of two Ï bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
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