反应详情

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-hydroxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (150 mg) is dissolved in tetrahydrofuran (3 ml), and thereto are added at room temperature potassium tert-butoxide (28 mg) and P-propiolactone (16 μl). The reaction solution is stirred overnight at room temperature, and then partitioned by adding ethyl acetate and 1N HCl. The organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→9:1) and LC/MS (CAPCEL PAK MGII (SHISEIDO), water:methanol=60:40→0:100, 40 ml/min) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(2-carboxyethoxy)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (12 mg). MS (m/z): 672 [M+H]+.

1. custompartitioned
2. additionby adding ethyl acetate and 1N HCl
3. washThe organic layer is washed with saturated brine
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→9:1) and LC/MS (CAPCEL PAK MGII (SHISEIDO), water:methanol=60:40→0:100, 40 ml/min)