Trifluoroacetic acid → 3-(4-Cyclohexylamino-2-methylsulfanyl-pyrimidin-5-yl)-3-oxo-propionic acid ethyl ester

참여 물질

반응 단계

Sodium hydride (60% dispersion in mineral oil, 6.07 g, 151.60 mmol) was added portionwise, under nitrogen atmosphere, at 0° C., to a mixture of benzotriazol-1-yl-(4-cyclohexylamino-2-methylsulfanyl-pyrimidin-5-yl)-methanone (25.4 g, 68.95 mmol) and tert-butyl ethyl malonate (14.36 mL, 75.83 mmol) in anhydrous DMF (400 mL) and the resulting mixture was stirred at RT for 15 h. The reaction mixture was poured into a mixture of NaHSO4 (aq 10%, 1 L) and ice (200 mL) and then was carefully extracted with EtOAc (2×200 mL). The combined organic extracts were washed with water (2×100 mL), dried over Na2SO4, filtered, and evaporated under reduced pressure. The yellow oil obtained was dissolved in DCM (30 mL) and trifluoroacteic acid (60 mL) was added. The reaction mixture was heated at reflux for 1 h. The resulting mixture was cooled and the solvent was evaporated under reduced pressure. NaHCO3 (sat'd aq) was added until pH 7 was reached and the resulting mixture was extracted with EtOAc (3×100 mL). The combined organic extracts were dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (EtOAc/hexane 10/90 to 15/85) to afford 20.9 g (90% yield) of 3-(4-cyclohexylamino-2-methylsulfanyl-pyrimidin-5-yl)-3-oxo-propionic acid ethyl ester.

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