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Synthesis of pyrimidine-based reference ligands. (a) methyl 4-methyl-3-oxopentanoate, NaOMe, MeOH, rt, overnight, 91–97%; (b) POCl3, reflux, 3 h, 86–87%; (c) t-butyl azetidin-3-yl(methyl)carbamate, DIPEA, dioxane, 150 °C, 30 min, μW, 34–38%; (d) HCl, dioxane, rt, 3 h-overnight, 77–90%; (e) H2CO, NaBH(OAc)3, DCM, rt, overnight, 82%; (f) 1-cyclobutylpiperazine, DIPEA, dioxane, 150 °C, 30 min, μW, 36–51%.
