Reaction Steps
tert-Butyl 3,3-dimethyl-2-oxo-6-(5-(tetrahydro-2H-pyran-4-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)indoline-1-carboxylate. A mixture of tris(dibenzylideneacetone)dipalladium(0) (0.099 g, 0.109 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.126 g, 0.217 mmol) in 1,4-dioxane (1.5 mL) was heated briefly with a heat gun until very hot and then added to tert-butyl 6-amino-3,3-dimethyl-2-oxoindoline-1-carboxylate (0.150 g, 0.543 mmol), 2-bromo-N-(tetrahydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-c]pyridin-5-amine (0.161 g, 0.543 mmol) and finely ground potassium carbonate (0.308 g, 2.226 mmol) in a sealable vessel with a stirbar. Nitrogen was blown in to blow out air. The resulting mixture was sealed, stirred vigorously, and heated at 100° C. for 4 h. After cooling to room temperature the reaction mixture was diluted with hot DMSO and filtered through a syringe filter. The filter cake was washed with hot DMSO. The filtrate was diluted with methanol and purified using reverse-phase preparatory HPLC (10-80% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 30 min). Fractions containing the desired product were combined, neutralized with saturated aqueous sodium bicarbonate, and the acetonitrile was removed on a rotary evaporator. The resulting mixture was extracted with ethyl acetate. The organics were dried over magnesium sulfate, filtered, concentrated on a rotary evaporator, and dried under high vacuum to give the desired product (0.148 g, 0.300 mmol, 55% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 9.63 (s, 1H), 8.47 (d, J=1.95 Hz, 1H), 7.38-7.47 (m, 2H), 7.27 (d, J=8.20 Hz, 1H), 6.74 (d, J=8.20 Hz, 1H), 6.29 (d, J=7.81 Hz, 1H), 6.07 (d, J=8.20 Hz, 1H), 3.87-3.97 (m, 2H), 3.73-3.87 (m, 1H), 3.42-3.55 (m, 2H), 2.01 (dd, J=2.34, 12.49 Hz, 2H), 1.63-1.74 (m, 2H), 1.61 (s, 9H), 1.32 (s, 6H); MS (ESI) m/z 493.2 [M+1]+.
