French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres

Process Development and Crystallization in Oiling-Out System of a Novel Topical Antiandrogen

An efficient route to (<i>S</i>)-<i>N</i>-(2-bromo-6-methoxypyridin-4-yl)-2-hydroxy-2,4-dimethylpentanamide <b>1</b>, a new topical antiandrogen, is described. The target compound has been manufactured on kilogram scale with an overall yield of 25% (HPLC purity 98.8% and >99% <i>ee</i>) from citrazinic acid. The key amide coupling between aminopyridine <b>4</b> and α-hydroxy-acid <b>6</b> was performed using a temporary protecting group to facilitate the acyl chloride formation. Aminopyridine <b>4</b> was manufactured from commercially available citrazinic acid via dibromide formation using phosphorus­(V) oxybromide followed by mono S_NAr reaction with sodium methoxide and a final Hofmann rearrangement. Enantiopure α-hydroxy-acid <b>6</b> was obtained using an enantioselective cyanosilylation followed by salt resolution with (<i>S</i>)-α-methyl benzylamine. The absolute configuration of compound <b>1</b> was determined with anomalous scattering and the final crystallization of API was performed after seeding a liquid–liquid mixture below the monotectic temperature and afforded a crystalline powder presenting a “desert rose” shape clusters

French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres