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Updated: Aug 17, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Efficient synthesis of a GABA A alpha2,3-selective allosteric modulator via a sequential Pd-catalyzed cross-coupling
Mark S Jensen1, R Scott Hoerrner, Wenjie Li
1Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. mark_jensen@merck.com
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 GABA(A) alpha(2/3)-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 for Pd removal in the final step is also described.
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