Efficient synthesis of a GABAA α2, 3-selective allosteric modulator via a sequential Pd-catalyzed cross-coupling approach

…, DP Nelson, GJ Javadi, PG Dormer, D Cai…

Index: Jensen, Mark S.; Hoerrner, R. Scott; Li, Wenjie; Nelson, Dorian P.; Javadi, Gary J.; Dormer, Peter G.; Cai, Dongwei; Larsen, Robert D. Journal of Organic Chemistry, 2005 , vol. 70, # 15 p. 6034 - 6039

Full Text: HTML

Citation Number: 41

Abstract

A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1, 2-a] pyrimidin-7-yl]- propan-2-ol (1), an oral GABAA α2/3-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method ...