A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK-8931)
| Autor: | Jacob H. Waldman, Thomas W. Lyons, Lu Chen, John R. Naber, Wenyong Chen, David A. Thaisrivongs, Baoyun Zhang, Zhiguo J. Song, Lushi Tan, William J. Morris, Jun Yang |
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| Rok vydání: | 2018 |
| Předmět: |
Molecular Structure
Thiadiazines 010405 organic chemistry Chemistry Organic Chemistry 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Catalysis Cyclic S-Oxides 0104 chemical sciences Aspartic Acid Endopeptidases Verubecestat Amyloid Precursor Protein Secretases Enzyme Inhibitors Physical and Theoretical Chemistry Copper |
| Zdroj: | Organic Letters. 20:1568-1571 |
| ISSN: | 1523-7052 1523-7060 |
| DOI: | 10.1021/acs.orglett.8b00259 |
| Popis: | The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights of which include the application of a continuous processing step to outcompete fast proton transfer in a Mannich-type ketimine addition, a copper-catalyzed amidation reaction, and an optimized guanidinylation procedure to form the key iminothiadiazine dioxide core. |
| Databáze: | OpenAIRE |
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