In a glass pressure tube was added 6-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (200 mg, 0.449 mmol), 4-(N,N-dimethylaminomethyl)phenylboronic acid pinacol ester hydrochloride (170 mg, 0.571 mmol), potassium phosphate (300 mg, 1.413 mmol), dioxane (12 mL) and water (3 mL). The suspension was stirred and purged with N2 then PdCl2(dppf)-CH2Cl2 adduct (50 mg, 0.061 mmol) was added. The reaction mixture was capped and stirred at 110° C. for 4 hr. The dark black reaction mixture was evaporated to dryness. The crude product was purified by silica gel chromatography (eluent: 0 to 70%, 20% (5% NH4OH in MeOH)/CH2Cl2) in CH2Cl2). The pure fractions were combined and evaporated to dryness to give the product as a very dark brown-black solid. The solid was taken up in CH2Cl2 and treated with Silicycle Si-Thiol (2 g, 1.46 mMol/g). After stirring for 30 minutes on a rotary evaporator (no vacuum) the mixture was filtered through a pad of Celite, washed with CH2Cl2, and evaporated to dryness. The light yellow colored solid was taken up in a small volume of MeOH and treated with 6 N HCl (200 uL) and re-evaporated to dryness. The residue was dissolved in a small volume of MeOH, ppt. with Et2O, triturated, filtered and dried under vacuum to give the product 6-{4-[(dimethylamino)methyl]phenyl}-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide hydrochloride salt as a light tan solid (205 mg, 85% yield). 1H NMR (400 MHz, DMSO-d6) δ=11.60 (br. s., 1H), 10.81 (br. s., 1H), 8.69 (t, J=4.9 Hz, 1H), 8.40 (s, 1H), 8.19 (s, 1H), 7.97 (d, J=8.3 Hz, 2H), 7.90 (d, J=1.0 Hz, 1H), 7.71 (d, J=8.3 Hz, 2H), 5.94 (s, 1H), 5.18 (dt, J=6.7, 13.2 Hz, 1H), 4.43 (d, J=4.8 Hz, 2H), 4.34 (d, J=5.3 Hz, 2H), 2.72 (d, J=5.1 Hz, 6H), 2.58-2.52 (m, 2H), 2.14 (s, 3H), 1.59-1.52 (m, 2H), 1.51 (d, J=6.6 Hz, 6H), 0.89 (t, J=7.3 Hz, 3H); LC-MS(ES)+ m/e 500.2 [M+H]+.
