Large-scale applications of transition metal-catalyzed couplings for the synthesis of pharmaceuticals.

Palladium-catalyzed coupling reactions have become a central tool for the synthesis of biologically active compounds both in academia and industry. Most of these transformations make use of easily available substrates and allow for a shorter and more selective preparation of substituted arenes and heteroarenes compared to non-catalytic pathways. Notably, molecular-defined palladium catalysts offer high chemoselectivity and broad functional group tolerance. Considering these advantages, it is not surprising that several palladium-catalyzed coupling reactions have been implemented in the last decade into the industrial manufacture of pharmaceuticals and fine chemicals. In this review different examples from 2001-2008 are highlighted, which have been performed at least on a kilogram scale in the chemical and pharmaceutical industries.

Recent Applications of Palladium-Catalyzed Coupling Reactions in the Pharmaceutical, Agrochemical, and Fine Chemical Industries

Novel pyrrolidine monomers bearing various functional groups are used to prepare oligomeric structures. The pyrrolidine monomers can be joined via standard phosphate linkages including phosphodiester, phosphorothioate, and phosphoramidate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding,

Pyrrolidine-containing monomers and oligomers

Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals

This review presents a comprehensive overview on selected synthetic routes towards commercial drug compounds as published in both journal and patent literature. Owing to the vast number of potential structures, we have concentrated only on those drugs containing five-membered heterocycles and focused principally on the assembly of the heterocyclic core. In order to target the most representative chemical entities the examples discussed have been selected from the top 200 best selling drugs of recent years.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-7-57.pdf

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals.

La synthese du (5S,S) methyl-2 diaza-2,5bicyclo [2.2.1] heptane et de son enantiomere est reportee

Fox Darrell E

Papers

Synthesis of (S,S)- and (R,R)-2-alkyl-2,5-diazabicyclo[2.2.1]heptanes

Azatetralone synthesis via regioselective grignard coupling and parham cyclization

A Practical Synthesis of N-Substituted Maleimides

Development of a Scaleable Process for the Synthesis of the A2a Agonist, UK-371,104

New Disulfide Route to 3-(1-Piperazinyl)-1,2-benzisothiazole. Nucleus for Atypical Antipsychotic Drugs