Nitrogen → N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-(4-pyridinyl)-1H-indazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (0.15 g, 0.359 mmol), 4-pyridinylboronic acid (0.088 g, 0.647 mmol) and potassium phosphate (tribasic) (0.229 g, 1.078 mmol) was added 1,4-dioxane (3 mL) and water (0.75 mL). The suspension was degassed with N2 for 10 min, at which time PdCl2(dppf)-CH2Cl2 (0.044 g, 0.054 mmol) was added and the sealed reaction heated at 100° C. overnight (reaction got very dark). Diluted reaction with EtOAc and filtered through Celite, washing with EtOAc and concentrated in vacuo to a residue that was dissolved in a minimum amount of DCM. Purification by silica gel chromatography (12 gram Isco GOLD silica column; Gradient B: 5-90%; A: dichloromethane, B: 10% (2 M ammonia in methanol) in chloroform) gave N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-(4-pyridinyl)-1H-indazole-4-carboxamide (112 mg, 0.264 mmol, 73.5% yield). 1H NMR (400 MHz, DMSO-d6) ppm 1.51 (d, J=6.57 Hz, 6H) 2.12 (s, 3H) 2.22 (s, 3H) 4.40 (d, J=4.80 Hz, 2H) 5.15-5.27 (m, 1H) 5.89 (s, 1H) 7.90-8.00 (m, 3H) 8.34 (s, 1H) 8.43 (s, 1H) 8.65-8.75 (m, 3H) 11.55 (s, 1H). MS(ES) [M+H]+ 416.1.

Provenance & Evidence