Sodium Bicarbonate → 1,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate

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Reaction Conditions

Reaction Steps

3-Bromofuro[3,2-c]pyridin-4-amine (310 mg, 1.455 mmol), 1,1-dimethylethyl 4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (577 mg, 1.589 mmol), PdCl2(dppf)-CH2Cl2 adduct (65 mg, 0.080 mmol), 1,4-Dioxane (15 mL), and saturated aqueous sodium bicarbonate (4.5 mL, 4.50 mmol) were added to a 200 mL flask equipped with a reflux condenser. The flask was evacuated and filled with nitrogen 4 times, and then the mixture was stirred at 100° C. under Nitrogen for 15 hours. LCMS showed complete and clean conversion, so it was cooled and filtered through celite, rinsing with EtOAc (50 mL). The filtrate was washed with half-saturated aqueous NaHCO3 (50 mL), and the aqueous phase was back-extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (1×100 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 60 g SiO2, 10%-75% EtOAc in hexanes gradient over 60 minutes) to give 1,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate (205 mg, 0.555 mmol, 38.1% yield) as an off-white solid. LC/MS (ES) m/z=370 [M+H]+

Provenance & Evidence