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

A Alimardanov, A Gontcharov, A Nikitenko…

Index: Alimardanov, Asaf; Gontcharov, Alexander; Nikitenko, Antonia; Chan, Anita W.; Ding, Zhixian; Ghosh, Mousumi; Levent, Mahmut; Raveendranath, Panolil; Ren, Jianxin; Zhou, Maotang; Mahaney, Paige E.; McComas, Casey C.; Ashcroft, Joseph; Potoski, John R. Organic Process Research and Development, 2009 , vol. 13, # 5 p. 880 - 887

Full Text: HTML

Citation Number: 3

Abstract

Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti (Oi-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 ...