Efficient synthesis of novel NK1 receptor antagonists: selective 1, 4-addition of grignard reagents to 6-chloronicotinic acid derivatives

F Hoffmann-Emery, H Hilpert, M Scalone…

Index: Hoffmann-Emery, Fabienne; Hilpert, Hans; Scalone, Michelangelo; Waldmeier, Pius Journal of Organic Chemistry, 2006 , vol. 71, # 5 p. 2000 - 2008

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Citation Number: 29

Abstract

A new efficient synthesis of two novel classes of NK1 receptor antagonists, among them befetupitant and netupitant, starting from 6-chloronicotinic acid is described. The introduction of the o-tolyl substituent at C (4) of the pyridine ring was achieved by a one-pot selective 1, 4- Grignard addition/oxidation sequence to 6-chloronicotinic acid or a derivative of it. The scope of this addition/oxidation sequence was examined. It was also shown that the ...