Synthesis of diethyl{[5-(3-fluorophenyl)-pyridine-2yl]methyl}phosphonate

US8329905B2 · kind B2 · utility

Assignee

• Merck Sharp & Dohme LLC · US

Inventors

• Kelvin Hin-Yeong Yong · Westfield, US
• Ilia Zavialov · Plainsboro, US
• Jianguo Yin · Plainsboro, US
• Xiaoyong Fu · Edison, US
• Thiruvettipuram K. Thiruvengadam · Kendall Park, US

Key dates

• Filing date: Feb 5, 2010
• Grant date: Dec 11, 2012
• Expiry date: Mar 7, 2031

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F9/58
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This application discloses a novel process for the preparation of phosphonate esters useful as intermediates in the preparation of himbacine analogs, themselves useful as thrombin receptor antagonists. The chemistry taught herein can be exemplified by the following scheme:wherein R9 is selected from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms, and R11 is selected independently for each occurrence from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms and hydrogen, X2 is Cl, Br, or I; X3 is selected from Cl and Br; and PdLn is a supported palladium metal catalyst or a soluble heterogeneous palladium catalyst. The L-derivatizing reagent is a moiety which converts the alcohol functional group of compound 137D to any leaving group which can be displaced by a triorgano-phosphite phosphonating agent.