Morpholine → (rac)-4-{4-Cyano-2-[phenylsulfonyl]phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

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Reaction Steps

The reaction was carried out under argon. Allyl 4-[4-cyano-2-(phenylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (220 mg, 0.378 mmol) and morpholine (1.5 eq., 43 mg, 0.567 mmol) were initially charged in dry THF (6 ml) at RT. The reaction mixture was degassed repeatedly (evacuation followed by venting with argon). Under protective gas, tetrakis(triphenylphosphine)palladium(0) (0.05 eq., 22 mg, 0.019 mmol) was added, and the reaction mixture was stirred at RT for 16 h (HPLC control). The mixture was then concentrated, and the residue was taken up in ethyl acetate (100 ml). The organic phase was washed successively with 0.1 N hydrochloric acid (6 ml), saturated ammonium chloride solution (3×50 ml), water (30 ml) and saturated sodium chloride solution (30 ml), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20). The target product was obtained as a solid (104 mg, 51% of theory).

Provenance & Evidence