Scheme 1. Synthesis of 5d.

(a) n-BuLi, 2,6-dichloro-3-isothiocyanatopyridine, THF, −78 °C; (b) Na₂CO₃, DMF, 90 °C, 83% (two steps); (c) bis(4-(di-tert-butylphosphino)-N,N-dimethylbenzenamine) palladium dichloride (2.5 mol %), 1-phenylvinylboronic acid, K₂CO₃, dioxane/water, 80 °C, 74%; (d) Me₃SOI, tBuOK, DMSO/THF, 75%; (e) 5 N HCl, THF, 65 °C, 93%; (f) methyl azetidine-3-carboxylate hydrochloride, AcOH, DIPEA, NaBH₃CN, MeOH/CH₂Cl₂, 75%; (g) NaOH/THF, then HCl and pH 6 sodium phosphate buffer, 86%.