Combinatorial synthesis of chemical building blocks 1. Azomethines
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Combinatorial synthesis of chemical building blocks 1. Azomethines Sergey V. Ryabukhin · Dmitriy M. Panov · Andrey S. Plaskon · Alexander Chuprina · Sergey E. Pipko · Andrey A. Tolmachev · Alexander N. Shivanyuk
Received: 5 June 2012 / Accepted: 8 October 2012 © Springer Science+Business Media Dordrecht 2012
Abstract 128 Azomethines were synthesized through condensation of carbonyl compounds with various amines in pyridine in the presence of Me3 SiCl as promoter and water scavenger in 58–98 % yield. Et3 N was added to reaction mixtures before precipitating the product with H2 O to prevent acid catalyzed hydrolysis of the C=N bond. The scope and limitation of the method are discussed. High yields and simple setup/workup procedure make this method suitable for the combinatorial synthesis of azomethines, which are suitable as starting materials for high throughput synthesis of various combinatorial libraries. The azomethines synthesized were used as starting materials in a one-pot combinatorial synthesis of amines and amides. Electronic supplementary material The online version of this article (doi:10.1007/s11030-012-9407-9) contains supplementary material, which is available to authorized users. S. V. Ryabukhin (B) Department of Chemistry, Kyiv National Taras Shevchenko University, 64 Volodymyrska Str., Kyiv 01601, Ukraine e-mail: [email protected] S. V. Ryabukhin · A. N. Shivanyuk The Institute of High Technologies, Kyiv National Taras Shevchenko University, 4 Glushkov Str., Building 5, Kyiv 03187, Ukraine D. M. Panov · A. S. Plaskon · S. E. Pipko · A. A. Tolmachev ChemBio Center, Kyiv National Taras Shevchenko University, 61 Chervonotkacka Str., Kyiv 02094, Ukraine D. M. Panov · A. S. Plaskon · A. Chuprina · S. E. Pipko · A. A. Tolmachev Enamine Ltd., 23 A. Matrosov Str., Kyiv 01103, Ukraine A. N. Shivanyuk The Institute of Pharmacology and Toxicology, The National Academy of Medicinal Sciences, 14 Ejen Pottier Str., Kyiv 03680, Ukraine e-mail: [email protected]
Keywords Aldehydes · Amines · Azomethines · Amides · Chlorotrimethylsilane · High throughput synthesis
Introduction Combinatorial synthesis of functional compounds is often based on the covalent attachment of several variable groups to a molecular scaffold through robust reactions of monofunctional and polyfunctional moderately reactive compounds (chemical building blocks). In this approach, the availability of appropriate building blocks determines the chemical diversity of target combinatorial libraries. Apparently, the chemical diversity of molecular arrays can be greatly increased through application of a combinatorial approach to the synthesis of chemical building blocks used in the final combinatorial synthetic step. Recently, we have developed a simple high throughput methodology for the synthesis of chemical building blocks [1] for the combinatorial synthesis of screening compounds. These efforts resulted in one of the world’s largest commercial collection of drug like screening compounds (1.8 million items) [2] and
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