Kilogram Scale Synthesis of the Pyrazinone Acetic Acid Core of an Orally Efficacious Thrombin Inhibitor

Abstract
A multi-kilogram scale synthesis of the orally efficacious thrombin inhibitor 1 has been achieved via construction of the pyrazinone core from an unsymmetric oxalic diamide. Key features include judicious choice of reagents to minimize side products, a key ruthenium catalyzed oxidation, and development of reaction conditions amenable to large-scale synthesis.

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