A Practical Enantioselective Synthesis of a Novel Peptide Deformylase Inhibitor
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- 作者：Joel Slade ; David Parker ; Michael Girgis ; Martin Mueller ; James Vivelo ; Hui Liu ; Joginder Bajwa ; Guang-Pei Chen ; Joseph Carosi ; Paul Lee ; Apurva Chaudhary ; Dana Wambser ; Kapa Prasad ; Kathryn Bracken
- 刊名：Organic Process Research & Development
- 出版年：2006
- 出版时间：January 2006
- 年：2006
- 卷：10
- 期：1
- 页码：78 - 93
- 全文大小：384K
- 年卷期：v.10,no.1(January 2006)
- ISSN：1520-586X
文摘
A practical synthesis of the peptide deformylase inhibitorLBM415, (2S)-N-(5-fluoro-1-oxido-2-pyridinyl)-1-[(2R)-2-[(formylhydroxyamino)methyl]-1-oxohexyl]-2-pyrrolidinecarboxamide,magnesium salt 11, is described. The key chiral intermediate,(2S)-N-(5-fluoro-2-pyridinyl)-1-[(2R)-2-[[formyl(phenylmethoxy)amino]methyl]-1-oxohexyl]-2-pyrrolidinecarboxamide 8, wasmade by coupling the corresponding amino acid 7 with thecarboxamide 25 prepared from L-proline and 2-amino-5-fluoropyridine. Following oxidation of the pyridine nitrogen,selective hydrogenolysis of the benzyl group afforded the freeacid of the drug substance, which was converted to themagnesium salt in situ with magnesium chloride. The productwas obtained in an overall yield of 16% with an ee > 99%.