1,4-Dioxane → HCID 178425143, compound

Participants

Reaction Conditions

Reaction Steps

To a 10 mL microwave vial were sequentially added 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.12 g, 0.321 mmol), 1,1-dimethylethyl 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate (0.138 g, 0.385 mmol), potassium phosphate (tribasic) (0.204 g, 0.963 mmol), 1,4-dioxane (3 mL), and water (0.75 mL). The stirring suspension was degassed with nitrogen for 10 min., wherein an emulsion had formed. Next added PdCl2(dppf)-CH2Cl2 adduct (0.039 g, 0.048 mmol) and the contents were placed onto a heat block and stirred at 105° C. overnight. After cooling to room temperature, the reaction mixture was diluted with EtOAc and filtered through Celite. The filter pad was washed with 50% THF/EtOAc. Silica gel was added to the combined filtrates and the mixture concentrated in vacuo to a solid. The contents were purified by silica gel chromatography (dry loaded, eluent: 5-80% gradient of DCM and chloroform containing 10% 2M Ammonia (in methanol)). The isolated solid was dried in vacuum oven at 45° C. overnight to afford the final product as 0.126 g (81%). LCMS E-S (M+H)=470.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.56 (d, J=6.57 Hz, 6H), 2.13 (s, 3H), 2.25 (s, 3H), 2.60 (s, 3H), 4.43 (d, J=5.05 Hz, 2H), 5.31-5.43 (m, 1H), 5.91 (s, 1H), 7.60 (d, J=8.84 Hz, 1H), 8.22 (s, 1H), 8.29-8.37 (m, 2H), 8.60 (s, 1H), 8.97 (t, J=5.05 Hz, 1H), 11.58 (br. s., 1H), 12.84 (s, 1H).

Provenance & Evidence