Water → (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyridin-4-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-iodopyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (250 mg) is dissolved in N,N-dimethylformamide (2 ml), then thereto are added pyridine-4-boronic acid (87 mg), tetrakis(triphenylphosphine)palladium (81 mg) and potassium carbonate (117 mg), and the mixture is stirred at 100° C. under nitrogen flow for 2 hours. After allowing to cool to room temperature, water is added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (NH-silica gel; hexane: ethyl acetate=4:1) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyridin-4-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (131 mg). MS (m/z): 661 [M+H]+

Provenance & Evidence