514829-77-7Relevant articles and documents
The use of glycidyl ethers involving aziridinium intermediates and other methodology for the preparation of enantiomerically pure drug candidates
Ayers, Timothy A.,Watson, Timothy J. N.,Subotkowski, Witold,Daniel, John,Webster, Mark
experimental part, p. 141 - 147 (2012/06/01)
An enantiospecific 1,2-amine migration process through an aziridinium intermediate involving ring-opening with potassium phthalimide derivatives to produce precursors to drug candidates was developed. The precursor amine derivatives were readily available by epoxide opening of simple glycidyl ether derivatives. The regioselectivity of the process was shown to provide approximately 85% of the desired rearranged product with subsequent conversion to the desired drug candidate occurring with excellent purity. An alternative approach using the same glycidyl ether derivatives as starting materials that overcame this regiochemical limitation was subsequently demonstrated.
Process improvements for the preparation of kilo quantities of a series of isoindoline compounds
Watson, Timothy J.,Ayers, Timothy A.,Shah, Nik,Wenstrup, David,Webster, Mark,Freund, David,Horgan, Stephen,Carey, James P.
, p. 521 - 532 (2013/09/05)
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.
