Cesium carbonate → (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-(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 (350 mg) is dissolved in 1,4-dioxane (1 ml), then thereto are added pyrrolidin-2-one (100 mg), tris(dibenzylideneacetone)-dipalladium (23 mg), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (21 mg) and cesium carbonate (241 mg) and the mixture is stirred at 100° C. under nitrogen flow overnight. 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, then thereto is added a small amount of NH-silica gel, the mixture is filtered, and the filtrate is concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=4:1) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-(pyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (105 mg). MS (m/z): 584 [M+H]+

Provenance & Evidence