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

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Reaction Steps

3-Bromofuro[3,2-c]pyridin-4-amine (7.23 g, 33.9 mmol), 1,1-dimethylethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (12.90 g, 37.4 mmol), PdCl2(dppf)-CH2Cl2 adduct (1.39 g, 1.702 mmol), 1,4-Dioxane (300 mL), and saturated aqueous sodium bicarbonate (100 mL, 100 mmol) were added to a 3-neck, 1 L flask equipped with a reflux condenser and a heating mantle. The flask was evacuated and filled with nitrogen 4 times, and then the mixture was stirred at reflux under Nitrogen for 2 hr. HPLC showed complete conversion, so it was cooled and allowed to stir at room temperature overnight. The crude mixture was then filtered through celite, rinsing with EtOAc (500 mL). The filtrate was washed with half-saturated aqueous NaHCO3 (500 mL), and the aqueous phase was back-extracted with ethyl acetate (1×500 mL). The combined organic phases was washed with brine (1×500 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 600 g SiO2, 20%-100% EtOAc in hexanes gradient over 60 minutes, then 100% EtOAc for 30 more minutes). The product fractions were combined and concentrated in vacuo to give 1,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate (9.23 g, 26.3 mmol, 77% yield) as an off-white solid. LC/MS (ES) m/z=352 [M+H]+.

Provenance & Evidence