1,4-Dioxane → 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-((dimethylamino)methyl)phenyl)-1H-indazole-4-carboxamide

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To a sealed tube were added 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.10 g, 0.226 mmol), N,N-dimethyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanamine (0.081 g, 0.271 mmol), and potassium phosphate (tribasic) (0.192 g, 0.902 mmol) followed by 1,4-Dioxane (2.0 mL) and water (0.5 mL). The suspension was stirred with degassing under N2 for 10 min, followed by addition of PdCl2(dppf)-CH2Cl2 adduct (0.018 g, 0.023 mmol). The reaction vessel was sealed and stirred with heating at 100° C. (heat block) for 2 h. The contents were allowed to stir with cooling to RT overnight. The mixture was diluted with EtOAc followed by addition of silica gel. The mixture was concentrated in vacuo and the obtained solid purified by silica gel chromatography (dry loaded, eluent: 8-95% gradient of chloroform (containing 10% 2M Ammonia in Methanol) and DCM. The collected product was concentrated from DCM/MTBE and then dried in vacuum oven for 16 h. The title compound was collected as an off-white solid (45 mg, 39%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.76 (m, 2H), 1.83-1.94 (m, 2H), 1.97-2.07 (m, 2H), 2.09-2.19 (m, 11H), 2.21 (s, 3H), 3.44 (s, 2H), 4.39 (d, J=4.80 Hz, 2H), 5.34 (quin, J=7.14 Hz, 1H), 5.88 (s, 1H), 7.41 (m, J=8.34 Hz, 2H), 7.81 (m, J=8.08 Hz, 2H), 7.87 (d, J=1.01 Hz, 1H), 8.12 (s, 1H), 8.36 (s, 1H), 8.65 (t, J=4.93 Hz, 1H), 11.53 (s, 1H); LC-MS (ES) m/z=498.3 [M+H]+

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