Sodium Bicarbonate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-(4-morpholinyl)-3-pyridinyl]-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) and [6-(4-morpholinyl)-3-pyridinyl]boronic acid (82 mg, 0.39 mmol) in DME/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 (10.76 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 and the insoluble mixture was heated in a microwave at 110° C. for 20 min. It was evaporated, 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 hexanes and dried to afford the title compound (123 mg, 89%) as a light beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.69 (d, J=2.27 Hz, 1H) 8.61 (t, J=4.93 Hz, 1H) 8.36 (s, 1H) 8.08-8.12 (m, 2H) 7.85 (d, J=1.01 Hz, 1H) 6.98 (d, J=8.84 Hz, 1H) 5.89 (s, 1H) 5.14 (quin, J=6.57 Hz, 1H) 4.39 (d, J=5.05 Hz, 2H) 3.71-3.75 (m, 4H) 3.50-3.55 (m, 4H) 2.22 (s, 3H) 2.13 (s, 3H) 1.50 (s, 3H) 1.49 (s, 3H). MS (ES) [M+H]+ 501.1.

Provenance & Evidence