Efficient synthesis of a GABA A alpha2,3-selective allosteric modulator via a sequential Pd-catalyzed cross-coupling approach

A practical synthesis of 2-3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo1,2-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.