Process Improvements for the Preparation of Kilo Quantities of a Series of Isoindoline Compounds

Autor:	David W. Freund, Mark Webster, Timothy A. Ayers, Timothy J. N. Watson, David L. Wenstrup, Stephen W. Horgan, Nik Shah, James P. Carey
Rok vydání:	2003
Předmět:	Phthalimides Indazole Stereochemistry Organic Chemistry Benzisoxazole Enantioselective synthesis Isoindoline Optically active Combinatorial chemistry chemistry.chemical_compound chemistry Obsessive compulsive SN2 reaction Physical and Theoretical Chemistry
Zdroj:	Organic Process Research & Development. 7:521-532
ISSN:	1520-586X 1083-6160
Popis:	A series of isoindoline analogues with either an indazole (HMR 2934, HMR 2651) or benzisoxazole (HMR 2543) appendage were prepared for the proposed treatment of psychiatric disorders such as obsessive compulsive disorder and attention deficit disorder. The isoindoline compounds were prepared by reduction of the corresponding phthalimides with LiAlH4. One compound was not chiral, and the other two required an enantioselective synthesis. The key step for these optically active analogues involved the coupling by an SN2 process of either a piperazynyl intermediate or a piperdinyl intermediate with methyl 3-benzyloxy-2-trifluoromethansulfonatopropionate. The products for these two analogues had >98% ee. Process improvements led to the multi-kilogram syntheses of each of these compounds.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6c1839c17be21d1f88b24d9482e980c3 https://doi.org/10.1021/op020225p Zobrazit plný text záznamu