Rho kinase inhibitor (ROCK) AR-13324 lowers the intraocular pressure (IOP) in both human and animal models of glaucoma by increasing the aqueous humor outflow through the trabecular meshwork, by reducing the fluid production and by reducing the episcleral venous pressure (EVP). A key step in the synthesis of AR13324 is coupling the (S)-3-(tert-butoxycarbonylamino)-2-(4-((2,4-dimethylbenzoyloxy) methyl)phenyl)propanoic acid with 6-aminoisoquionline. 6-Aminoisoquinoline, in turn, is prepared in 3 steps from 2-(carboxymethyl)-4-nitrobenzoic acid (1). The final step involves a 4-part reduction of 1,3-dichloro-nitroisoquinoline (3) using Pd/C and either hydrogen or hydrazine. To better understand this synthesis, and to identify the intermediates formed in the reaction towards 6-aminoisoquinoline, this step was studied in detail.

Identification of intermediates in the stepwise reduction of 1,3-dichloro-6-nitroisoquinoline to 6-aminoisoquinoline

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.