Pilot-plant preparation of an αvβ3 integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling

Jerry D. Clark, D. Keith Anderson, David V. Banaszak, Derek B. Brown, Ann M. Czyzewski, Albert D. Edeny, Puneh S. Forouzi, Donald J. Gallagher, V. H. Iskos, H. Peter Kleine, Carl M. Knable, Melissa K. Lantz, Mark A. Lapack, Christine M.V. Moore, Frank W. Muellner, James B. Murphy, Carlos A. Orihuela, Mark A. Pietz, Thomas E. Rogers, Peter G. RuminskiHarish K. Santhanam, Tobin C. Schilke, Ajit S. Shah, Ahmad Y. Sheikh, Gerald A. Weisenburger, Bruce E. Wise

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Studies directed toward the process research, development, and scale-up preparation of the potential αvβ3 integrin antagonist 1 are described. A convergent approach is detailed wherein tetrahydropyrimidine hydroxybenzoic acid 2 is linked to the β-amino acid ester 3 via a diisoproylcarbodiimide, catalytic HOBt coupling reaction. Saponification of the resulting ethyl ester, isolation of the corresponding zwitterion, H3PO4 salt formation, crystallization, and acetonitrile-to-acetone exchange give rise to 1 as a crystalline monohydrate in 67% overall yield from 4.

Original languageEnglish
Pages (from-to)1088-1093
Number of pages6
JournalOrganic Process Research and Development
Volume13
Issue number6
DOIs
StatePublished - Nov 20 2009

Fingerprint

Dive into the research topics of 'Pilot-plant preparation of an αvβ3 integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling'. Together they form a unique fingerprint.

Cite this