Sodium Bicarbonate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-(2-oxo-2,3-dihydro-1H-benzimidazol-5-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 (100 mg, 0.24 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2H-benzimidazol-2-one (93 mg, 0.36 mmol) in dioxane/water (3 mL: 1 mL). PdCl2(dppf)-CH2Cl2 (9.8 mg, 0.012 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (60.4 mg, 0.72 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 130° C. for 20 min. DCM/MeOH (1:1) was added, it was pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH). Fractions were evaporated. EtOH was added, it was sonicated and the solids that precipitated were filtered, washed with EtOH and DCM and dried to afford the title compound (43 mg, 37%) as a beige solid. 1H NMR (400 MHz, DMSO-d6) ppm 11.53 (s, 1H) 10.78 (s, 1H) 10.74 (s, 1H) 8.64 (t, J=4.80 Hz, 1H) 8.35 (s, 1H) 8.02 (s, 1H) 7.81 (s, 1H) 7.44 (dd, J=8.08, 1.77 Hz, 1H) 7.36-7.39 (m, 1H) 7.03 (d, J=8.08 Hz, 1H) 5.89 (s, 1H) 5.16 (quin, J=6.57 Hz, 1H) 4.39 (d, J=4.80 Hz, 2H) 2.21 (s, 3H) 2.13 (s, 3H) 1.50 (s, 3H) 1.49 (s, 3H). MS(ES) [M+H]+ 471.3

Provenance & Evidence