Sodium Bicarbonate → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-6-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

In a 25 mL sealable tube under nitrogen were combined 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (110 mg, 0.26 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (82 mg, 0.4 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (10.8 mg, 0.013 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (66.4 mg, 0.79 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 100° C. for 20 min. The mixture was evaporated, DCM/MeOH (1:1) was added, and the contents pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in EtOAc along with some hexanes, it was sonicated, and the solids that precipitated were filtered. Acetonitrile was added, solids that precipitated were filtered, and further washed with acetonitrile/ether (2:8) and dried to afford the title compound as an off-white solid (84 mg, 76%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.48 (t, J=4.93 Hz, 1H) 8.31 (s, 1H) 8.26 (s, 1H) 8.04 (s, 1H) 8.03 (s, 1H) 7.81 (d, J=1.01 Hz, 1H) 5.90 (s, 1H) 5.06 (quin, J=6.57 Hz, 1H) 4.39 (s, 1H) 4.38 (s, 1H) 3.90 (s, 3H) 2.23 (s, 3H) 2.13 (s, 3H) 1.50 (s, 3H) 1.48 (s, 3H); LC-MS (ES) m/z=419.0

Provenance & Evidence