Practical Asymmetric Synthesis of a Potent Cathepsin K Inhibitor. Efficient Palladium Removal Following Suzuki Coupling
- 4 March 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 68 (7) , 2633-2638
- https://doi.org/10.1021/jo0205614
Abstract
A large-scale, chromatography-free synthesis of a potent and selective Cathepsin K inhibitor 1 is reported. The key asymmetric center was installed by addition of (R)-pantolactone to the in situ-generated ketene 4a. The final step of the convergent synthesis of 1 was completed via Suzuki coupling of aryl bromide 7a with unprotected aryl piperazine boronic acid 13. Residual palladium and iron generated in the Suzuki coupling were efficiently removed from crude 1 via a simple extractive workup using lactic acid.Keywords
This publication has 18 references indexed in Scilit:
- Bis(pyrimidine)-based palladium catalysts: synthesis, X-ray structure and applications in Heck–, Suzuki–, Sonogashira–Hagihara couplings and amination reactionsJournal of Organometallic Chemistry, 2001
- Silica-supported imine palladacycles—recyclable catalysts for the Suzuki reaction?Journal of Organometallic Chemistry, 2001
- An easily prepared, air and moisture stable, resin-bound palladium catalyst for Suzuki cross-coupling reactionsTetrahedron Letters, 1999
- Removal of Palladium from Organic Reaction Mixtures by TrimercaptotriazineOrganic Process Research & Development, 1997
- Polymer-bound palladium-catalyzed cross-coupling of organoboron compounds with organic halides and organic triflatesTetrahedron Letters, 1997
- Proteolytic Activity of Human Osteoclast Cathepsin KJournal of Biological Chemistry, 1996
- Human Cathepsin O2, a Matrix Protein-degrading Cysteine Protease Expressed in OsteoclastsJournal of Biological Chemistry, 1996
- Palladium-Catalyzed Cross-Coupling Reactions of Organoboron CompoundsChemical Reviews, 1995
- Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor AntagonistThe Journal of Organic Chemistry, 1994
- Tartaric acid, an efficient chiral auxiliary: new asymmetric synthesis of 2-alkyl-2-arylacetic acidsThe Journal of Organic Chemistry, 1987