A suspension of 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (160 mg, 0.63 mmol), 3-bromo-4-methyl-5-(prop-1-ynyl)pyridine (Intermediate 45, 66 mg, 0.31 mmol) and potassium acetate (93 mg, 0.94 mmol) in dioxane (3 mL) was degassed with a stream of argon for a couple of min. PdCl2(dppf) CH2Cl2 (13 mg, 0.02 mmol) was added and the mixture was heated at reflux under N2 for 4 h. The mixture was allowed to cool, filtered and concentrated in vacuo. The obtained residue (80 mg, 4-methyl-3-(prop-1-ynyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine) was mixed with sodium tetrachloropalladate(II) (4 mg, 0.01 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (6 mg, 0.02 mmol), and (1r,4r)-6′-bromo-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 19, 90 mg, 0.24 mmol) in dioxane (3 mL). The mixture was degassed with a stream of argon for a couple of min. and then heated at reflux. The reaction mixture was allowed to cool and the solvent was removed in vacuo. The residue was partitioned between water and EtOAc. The organic phase was dried (Na2SO4) and evaporated to give a crude product which was purified by flash chromatography (4 g SiO2, heptane-(EtOAc/MeOH/NH3 90:10:1) gradient. The obtained material was purified by preparative chromatography. Fractions containing the product were pooled and the organic solvent was removed in vacuo. The residue was partitioned between 1 M NaOH and EtOAc. The organic phase was dried (Na2SO4) and evaporated to give an oily residue which was solidified by co-evaporation with acetonitrile to give the title compound (15 mg, 15% yield) after drying in vacuo at 40° C.: 1H NMR (400 MHz, DMSO-d6) δ ppm 0.98 (t, 1 H), 1.11-1.34 (m, 2 H), 1.34-1.57 (m, 3 H), 1.83 (d, 2 H), 2.13 (m, 9 H), 2.87-3.13 (m, 3 H), 3.20 (s, 3 H), 6.50 (d, 3 H), 7.18 (d, 1 H), 7.39 (d, 1 H), 8.16 (br. s., 1 H), 8.46 (br. s., 1 H); MS (APCI+) m/z 427 [M+H]+.
