Synthetic method and applications of polysubstituted pyridine derivative

Abstract

The invention belongs to the field of organic chemical synthesis, and relates to a synthetic method and applications of a polysubstituted pyridine derivative. According to the method, a 2,3-triazine compound and a ketone compound are used as reaction substrates, and can be subjected to a one-step reaction under the action of a catalytic amount of an alkali to synthesize polysubstituted pyridine, wherein the reaction does not involve in the use of danger and controlled drugs, so that a simple, safe, efficient and environment-friendly way is provided for synthesis of polysubstituted pyridine. According to the invention, the reaction can also be used for synthesis of drug molecules, such as one-step synthesis of drug molecule etoricoxib and a derivative thereof; and the product obtained by the invention is further derivatized to obtain multiple types of pyridine functional group-containing active molecules, such as two-step synthesis of active molecules 2-SORA.

Description

technical field [0001] The invention belongs to the field of organic synthetic chemistry, and specifically relates to a synthesis method and application of a multi-substituted pyridine derivative. Background technique [0002] Pyridine is the simplest nitrogen-containing aromatic heterocyclic structure, which also means that pyridine compounds are the most ubiquitous and important class of nitrogen-containing aromatic heterocyclic compounds. This structural unit widely exists in many natural products, drugs, bioactive molecules, organic catalysts and ligands, and is of great scientific significance. [0003] C3, C5 substituted pyridine derivatives are ubiquitous in natural products containing pyridine structures, drug molecules and active molecules, for example, the marketed drug Etoricoxib and effective orexin 2 receptor antagonists contain 2, 3-disubstituted or 2,3,5-trisubstituted pyridine, in these important drug molecules and biologically active molecules, no matter wh...

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Problems solved by technology

[0003] C3, C5 substituted pyridine derivatives are ubiquitous in natural products containing pyridine structures, drug molecules and active molecules, such as the marketed drug etoricoxib (Etoricoxib ) and effective orexin 2 receptor antagonists contain 2,3-disubstituted or 2,3,5-trisubstituted pyridine, in these important drug molecules and bioactive molecules, no matter which substituent is First introduced, it will be difficult to selectively realize the subsequent transformation due to the influence of unfavorable destination effect or electronic effect. Compared with the C2, C4 and C6 positions of pyridine, the direct functionalization of C3 and C5 of pyridine is more challenging

[0004] For this reason, Boger (Boger, D.L. Chem. Rev. 1986, 86, 781), Okatani (Okatani, T.; Koyama, J.; Tagahara, K. Heterocycles 1989 , 29, 1809), Igeta (Igeta, H.Chem.Pharm.Bull.1985, 33, 3050.) and Neunhoeffer (Neunhoeffer, H.; Clausen, M.; Voetter, H.; Ohl, H.; Krueger, C.; Angermund, K.Liebigs Ann.Chem.1985,1732.) etc. have made pioneering contributions, they can prepare C3, C5 substituted pyridine derivatives from triazine, this synthetic method greatly improves It is of great significance to improve the synthesis efficiency of aromatic heterocyclic molecules, but unfortunately, in these research work, it is necessary to use highly active and difficult-to-prepare molecules, such as enamines, alkyneamines, etc. These active components need to be tedious The synthesis process, coupled with the high requirements for storage and transportation, makes this reaction method difficult to realize

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