Synthesis of a Nucleoside Phosphoramidate Prodrug Inhibitor of HCV NS5B Polymerase: Phenylboronate as a Transient Protecting Group
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- 作者：Benjamin A. Mayes ; Jeevanandam Arumugasamy ; Erkan Baloglu ; David Bauer ; Alan Becker ; Narayan Chaudhuri ; G. Mark Latham ; Jie Li ; Steve Mathieu ; F. Patrick McGarry ; Elodie Rosinovsky ; Alistair Stewart ; Christophe Trochet ; Jingyang Wang ; Adel Moussa
- 刊名：Organic Process Research & Development
- 出版年：2014
- 出版时间：June 20, 2014
- 年：2014
- 卷：18
- 期：6
- 页码：717-724
- 全文大小：309K
- 年卷期：v.18,no.6(June 20, 2014)
- ISSN：1520-586X
文摘
A synthetic process for 2鈥?C-methylcytidine-5鈥?[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl-N-benzylphosphoramidate], a nucleotide prodrug inhibitor of hepatitis C virus NS5B polymerase, is described. The route developed was demonstrated on 100 g scale and featured the key application of phenylboronic acid as an effective transient means to protect the 2鈥?3鈥?hydroxyls of 2鈥?C-methylcytidine. This synthetic methodology resulted in a reduction in the number of isolations from five to two and an increase in the overall yield by 50% relative to the original unscalable discovery route. The synthesis and characterization of 2鈥?C-methylcytidine-2鈥?3鈥?O-phenylboronate is also provided.