tert-Butyl 5-{[(trifluoromethyl)sulfonyl]oxy}-3,3a,4,6a-tetrahydrocyclopenta-[c]pyrrole-2(1H)-carboxylate (8-2, 1 g, 2.7 mmol, 1.0 equiv), bis(pinocolato)diboron (0.75 g, 3.0 mmol, 1.1 equiv), potassium acetate (0.8 g, 8.4 mmol, 3.0 equiv) and PdCl2(dppf) (0.144 g, 0.196 mmol, 0.07 equiv) were added to anhydrous 1,4-dioxane (4 mL) and heated to 60° C. After 18 h, the reaction contents were cooled to RT, followed by the subsequent addition of water (1.4 mL), 5-Chloro-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (6-1, 766 mg, 2.8 mmol, 1.0 equiv), Cs2CO3 (1.8 g, 5.5 mmol, 2.00 equiv) and Bis(tri-tert-butylphosphine)palladium(0) (0.186 g, 0.364 mmol, 0.13 equiv). The resulting mixture was heated to 60° C. for 4.5 h. Following this duration, LCMS showed consumption of starting material. The contents were then cooled to room temperature, diluted with ethyl acetate (50 mL), filtered through Celite and rinsed with ethyl acetate (3×50 mL) and water (1×30 mL). The filtrate layers were separated and the combined organics were washed with saturated NaHCO3 (100 mL). The combined aqueous layers were then back-extracted with ethyl acetate (2×50 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a dark orange oil. Purification by normal-phase chromatography (0-50% EtOAc:Hex) afforded 14-1 as an off-white solid. MS m/z (M+H): calculated=447.2; observed=447.2.
