Modified Knorr pyrrole synthesis

A modified Knorr pyrrole synthesis was key to a practical synthesis of the potent 5-opioid agonist SB-342219 by GSK. SB-342219 is a selective 5-opioid agonist undergoing preclinical evaluation for the potential treatment of neuropathetic pain. The medicinal chemistry route used the conventional Knorr pyrrole synthesis. Condensation of the ketone with a-aminoketone, which was generated in situ by reduction of the requisite phenylhydrazone using zinc, gave the desired pyrrole in 63% yield. 

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