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

Participants

Reaction Steps

6-bromo-N-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide (80 mg, 0.19 mmol), N,N-dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethanamine (84 mg, 0.29 mmol) and PdCl2(dppf)-CH2Cl2 adduct (7.8 mg, 0.009 mmol) in dioxane/water (3 ml:1 ml) were stirred for 10 min under nitrogen. Sodium bicarbonate (48.3 mg, 0.58 mmol) was added and the insoluble mixture was irradiated in a microwave at 100° C. for 20 min. The reaction mixture was evaporated, dissolved in DCM/MeOH (1:1), and preabsorbed on silica gel and purified using silica gel chromatography (eluent: DCM/MeOH/NH4OH; gradient 0 to 80:20:2 in DCM). The isolated product was dissolved in hot DMSO/MeOH and purified using reversed-phase HPLC (25-80% gradient of MeCN in water with 0.1% TFA). Most of the solvent from the combined product fractions were evaporated and sat. sol. NaHCO3 was added, solids that crashed out were filtered, air-dried for 15 min, and dried in vacuum-oven overnight. The product was collected as a white solid (56 mg, 56%). 1H NMR (400 MHz, DMSO-d6)™ ppm 11.54 (br. s., 1H) 8.64 (t, J=4.80 Hz, 1H) 8.35 (s, 1H) 8.05 (s, 1H) 7.81-7.84 (m, 2H). LC-MS (ES) m/z=528.1 [M+H]+

Provenance & Evidence