22287-35-0Relevant academic research and scientific papers
Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry
Kokhan, Serhii O.,Valter, Yevheniia B.,Tymtsunik, Andriy V.,Komarov, Igor V.,Grygorenko, Oleksandr O.
, p. 6450 - 6456 (2017/12/01)
Syntheses of bicyclo[1.1.1]pentane-derived azides and terminal alkynes – interesting substrates for click reactions – are described. With a few exceptions, these compounds were prepared in two or three steps starting from common synthetic intermediates – the corresponding carboxylic acids. The key step in the synthesis of 1-azidobicyclo[1.1.1]pentanes is a copper-catalysed diazo-transfer reaction with imidazole-1-sulfonyl azide. The preparation of bicyclo[1.1.1]pentyl-substituted alkynes relies on a Seyferth–Gilbert homologation with dimethyl 1-diazo-2-oxopropylphosphonate (Ohira–Bestmann reagent). Both types of target compounds were found to be suitable substrates for click reactions, and thus they are promising building blocks for medicinal, combinatorial and bioconjugate chemistry. A practically important side result of this study was a multigram preparation of Boc-monoprotected 1,3-diaminobicyclo[1.1.1]pentane – a representative bicyclic conformationally restricted diamine derivative.
Organic chemistry: Strain-release amination
Gianatassio, Ryan,Lopchuk, Justin M.,Wang, Jie,Pan, Chung-Mao,Malins, Lara R.,Prieto, Liher,Brandt, Thomas A.,Collins, Michael R.,Gallego, Gary M.,Sach, Neal W.,Spangler, Jillian E.,Zhu, Huichin,Zhu, Jinjiang,Baran, Phil S.
, p. 241 - 246 (2016/01/25)
To optimize drug candidates, modern medicinal chemists are increasingly turning to an unconventional structural motif: small, strained ring systems. However, the difficulty of introducing substituents such as bicyclo[1.1.1]pentanes, azetidines, or cyclobutanes often outweighs the challenge of synthesizing the parent scaffold itself. Thus, there is an urgent need for general methods to rapidly and directly append such groups onto core scaffolds. Here we report a general strategy to harness the embedded potential energy of effectively spring-loaded C-C and C-N bonds with the most oft-encountered nucleophiles in pharmaceutical chemistry, amines. Strain-release amination can diversify a range of substrates with a multitude of desirable bioisosteres at both the early and late stages of a synthesis. The technique has also been applied to peptide labeling and bioconjugation.
PROPELLANE DERIVATES AND SYNTHESIS
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Paragraph 0100, (2015/09/28)
Disclosed herein are compounds of the general Formula (I), and methods of synthesizing substituted bicyclo[1.1.1 jpentanes. The synthetic methods described herein use a [1.1.1]propellane, a Group VIII transition metal compound, a hydride source and a reagent that can contribute a substituent to form a substituted bicycIo[1.1.1 ]pentane, such as a compound of the general Formula (I).
A new route to bicyclo[1.1.1]pentan-1-amine from 1-azido-3-iodobicyclo[1.1. 1]pentane
Goh, Yi Ling,Tam, Eric K.W.,Bernardo, Paul H.,Cheong, Choon Boon,Johannes, Charles W.,William, Anthony D.,Adsool, Vikrant A.
supporting information, p. 1884 - 1887 (2014/05/06)
From a medicinal chemistry perspective, bicyclo[1.1.1]pentan-1-amine (1) has served as a unique and important moiety. Synthetically, however, this compound has received little attention, and only one scalable route to this amine has been demonstrated. Reduction of an easily available and potentially versatile intermediate, 1-azido-3-iodobicyclo[1.1.1]pentane (2), can offer both a flexible and scalable alternative to this target. Herein, we describe our scrutiny of this reportedly elusive transformation and report our ensuing success with this endeavor.
FUSED FURANS FOR THE TREATMENT OF HEPATITIS C
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Page/Page column 68-69, (2014/10/15)
The disclosure provides compounds of formula I or II, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV. [
Scalable synthesis of 1-bicyclo[1.1.1]pentylamine via a hydrohydrazination reaction
Bunker, Kevin D.,Sach, Neal W.,Huang, Qinhua,Richardson, Paul F.
supporting information; experimental part, p. 4746 - 4748 (2011/10/13)
The reaction of [1.1.1]propellane with di-tert-butyl azodicarboxylate and phenylsilane in the presence of Mn(dpm)3 to give di-tert-butyl 1-(bicyclo[1.1.1]pentan-1-yl)hydrazine-1,2-dicarboxylate is described. Subsequent deprotection gives 1-bicyclo[1.1.1]pentylhydrazine followed by reduction to give 1-bicyclo[1.1.1]pentylamine. The reported route marks a significant improvement over the previous syntheses of 1-bicyclo[1.1.1] pentylamine in terms of scalability, yield, safety, and cost.
