Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications

Autor:	Ren Jianxin, Gontcharov Alexander, John R. Potoski, Zhixian Ding, Asaf Alimardanov, Paige E. Mahaney, Casey Cameron Mccomas, Antonia Nikitenko, Joseph Ashcroft, Mousumi Ghosh, Panolil Raveendranath, Levent Mahmut, Chan Anita Wai-Yin, Maotang Zhou
Rok vydání:	2009
Předmět:	Amidine chemistry.chemical_compound chemistry Norepinephrine transporter biology Stereochemistry Organic Chemistry Side product Diol biology.protein Lewis acids and bases Physical and Theoretical Chemistry
Zdroj:	Organic Process Research & Development. 13:880-887
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op900141r
Popis:	Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)4 as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation−methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::999ca2acb0b5d4027551d44f8585a793 https://doi.org/10.1021/op900141r Zobrazit plný text záznamu