Development of a Scalable Synthesis of a Serotonin Receptor Antagonist

Autor:	Frank Schaefer, Michael J. Girgis, Mahavir Prashad, Bin Hu, Wen-Chung Shieh, Yugang Liu
Rok vydání:	2014
Předmět:	Active ingredient chemistry.chemical_compound chemistry Reagent Organic Chemistry Side product Anhydrous Organic chemistry Serotonin receptor antagonist Physical and Theoretical Chemistry Adduct Methyl iodide
Zdroj:	Organic Process Research & Development. 19:290-295
ISSN:	1520-586X 1083-6160
Popis:	An efficient process was developed for the manufacture of MSA100, a serotonin receptor antagonist, via a five-step synthetic route furnishing a high quality of active pharmaceutical ingredient. Highlights of this synthesis include: (1) replacing carcinogenic methyl iodide with methyl p-toluenesulfonate as the methylating reagent; (2) a hydrogenation protocol with optimized temperature, pressure, and mass-transfer conditions that avoided one side product and reduced the other one effectively; (3) chemical resolution employing D-camphoric acid in a mixed-solvent system; (4) amidation under anhydrous conditions for controlling a Michael adduct impurity; and (5) plausible mechanisms for the formation of side products.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::14b0af8335f0194b8ea54a773c05652d https://doi.org/10.1021/op5003402 Zobrazit plný text záznamu