1196152-34-7Relevant academic research and scientific papers
METHOD FOR SYNTHESIZING ENANIOMERICALLY PURE N-(PYRIDIN-4-YL)-2-HYDROXY-ALKYLAMIDE DERIVATIVES
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Paragraph 0220; 0221; 0222, (2019/01/25)
The present invention relates to a novel process for preparing enantiomerically pure compounds of N-(pyrid-4-yl)-2-hydroxyalkylamide type corresponding to the general formula (C) below: and also to processes for preparing the reaction intermediates used i
Process Development and Crystallization in Oiling-Out System of a Novel Topical Antiandrogen
Daver, Sébastien,Rodeville, Nicolas,Pineau, Francois,Arlabosse, Jean-Marie,Moureou, Christine,Muller, Franck,Pierre, Romain,Bouquet, Karinne,Dumais, Laurence,Boiteau, Jean-Guy,Cardinaud, Isabelle
, p. 231 - 240 (2017/02/26)
An efficient route to (S)-N-(2-bromo-6-methoxypyridin-4-yl)-2-hydroxy-2,4-dimethylpentanamide 1, 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% ee) from citrazinic acid. The key amide coupling between aminopyridine 4 and α-hydroxy-acid 6 was performed using a temporary protecting group to facilitate the acyl chloride formation. Aminopyridine 4 was manufactured from commercially available citrazinic acid via dibromide formation using phosphorus(V) oxybromide followed by mono SNAr reaction with sodium methoxide and a final Hofmann rearrangement. Enantiopure α-hydroxy-acid 6 was obtained using an enantioselective cyanosilylation followed by salt resolution with (S)-α-methyl benzylamine. The absolute configuration of compound 1 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.
