Reaction Steps
A mixture of tert-butyl 2′-(2-chloropyrimidin-4-yl)-5′-(4-methoxybenzyl)-4′-oxo-1′,4′,5′,6′-tetrahydrospiro[piperidine-4,7′-pyrrolo[3,2-c]pyridine]-1-carboxylate (A5) (4.5 g, 8.36 mmol), 2-benzofuranboronic acid (4.06 g, 25.09 mmol) and potassium phosphate tribasic heptahydrate (8.49 g, 25.09 mmol) was dissolved in anhydrous dioxane (105 mL). The resulting solution was purged with nitrogen, followed by addition of 1,1′-bis(diphenylphosphino)ferrocene palladium(II)chloride (676 mg, 0.836 mmol). The resulting mixture was again purged with nitrogen and stirred at 140° C. for 45 min in the microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc, washed three times with aqueous NaHCO3, once with brine, dried over Na2SO4, filtered and concentrated under vacuum. The crude product was triturated with toluene which gave tert-butyl 2′-(2-(benzofuran-2-yl)pyrimidin-4-yl)-5′-(4-methoxybenzyl)-4′-oxo-1′,4′,5′,6′-tetrahydrospiro[piperidine-4,7′-pyrrolo[3,2-c]pyridine]-1-carboxylate (A6) as a white solid (3.60 g, 70%). 1H NMR (400 MHz, DMSO-D6, 300K): δ=1.42 (9H, s), 1.55 (2H, br d, J=13.0 Hz), 2.08 (2H, br dt, J=13.4 Hz), 2.65 (2H, br s), 3.56 (2H, br s), 3.74 (3H, s), 3.80 (2H, br s), 4.57 (2H, br s), 6.92 (2H, d, J=8.6 Hz), 7.31 (2H, d, J=8.6 Hz), 7.35 (1H, t, J=7.6 Hz), 7.43 (1H, s), 7.46 (1H, t, J=7.8 Hz), 7.75 (1H, d, J=8.2 Hz), 7.80 (1H, d, J=5.5 Hz), 7.82 (1H, d, J=7.7 Hz), 8.03 (1H, s), 8.77 (1H, d, J=5.4 Hz), 11.75 (1H, s). MS (ES) C36H37N5O5 requires: 619. found: 620.2 [M+H]+.
