Efficient Synthesis of a GABA_A alpha_(2,3)-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach

摘要

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