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

MS Jensen, RS Hoerrner, W Li, DP Nelson…

Index: Li, Wenjie; Nelson, Dorian P.; Jensen, Mark S.; Hoerrner, R. Scott; Cai, Dongwei; Larsen, Robert D.; Reider, Paul J. Journal of Organic Chemistry, 2002 , vol. 67, # 15 p. 5394 - 5397

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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 ...