1,4-Dioxane → 1-cyclopropyl-6-{4-[(dimethylamino)methyl]phenyl}-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a 20 mL microwave vial containing a mixture of 6-bromo-1-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.070 g, 0.169 mmol), N,N-dimethyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanamine (0.060 g, 0.202 mmol), and potassium phosphate (tribasic) (0.107 g, 0.506 mmol) were added 1,4-dioxane (2.0 mL) and water (0.5 mL). The suspension was stirred with degassing under N2 for 10 min. (emulsion), and then PdCl2(dppf)-CH2Cl2 adduct (0.021 g, 0.025 mmol) was added. The contents were sealed and heated at 100° C. (heat block) for 2 h. After cooling to RT, the reaction mixture was diluted with EtOAc. Silica gel was added the mixture was concentrated in vacuo to dryness. The contents were purified by silica gel chromatography (dry loaded, eluent: 8-95% gradient chloroform (containing 10% 2M Ammonia in Methanol) and DCM). The collected product was concentrated from MTBE and dried in a vacuum oven for 2 h. The title compound was collected as a white solid (67 mg, 81%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-1.20 (m, 4H), 2.12 (s, 3H), 2.15-2.24 (m, 9H), 3.44 (s, 2H), 3.87 (t, J=5.31 Hz, 1H), 4.38 (d, J=4.80 Hz, 2H), 5.88 (s, 1H), 7.42 (m, J=8.34 Hz, 2H), 7.80 (m, J=8.08 Hz, 2H), 7.90 (s, 1H), 8.04 (s, 1H), 8.31 (s, 1H), 8.67 (t, J=4.93 Hz, 1H), 11.53 (s, 1H); LC-MS(ES) m/z=470.3 [M+H].

Provenance & Evidence