CJ-15161

An efficient four-step sequence has been developed for the synthesis of the κ-opioid receptor agonist I (CJ-15,161).The process features four consecutive regioselective and stereospecific inversions at a single aziridinium stereogenic center, which leads to overall retention of stereochem., in a single operation.The chem. is straightforward, practical and amenable to large-scale synthesis.Crystal structure of suitable for formulation polymorph benzoate salt form of I is also reported.

Syntheses of CJ-15,161 (1) involving intermolecular N-arylation of an appropriately functionalized diamine, obtained from the precursor alpha-amino acids or, more conveniently, from the corresponding 1,2-amino alcohols via 1,2,3-oxathiazolidine-2,2-dioxide 22, are reported.