Diisopropylethylamine → (2R,3R)-4-(2-Chlorophenyl)-3-[4-ethyl-3-(6-methyl-2,4-dioxo-1,4-dihydro-2H-thieno[2,3-d]pyrimidin-3-yl)-benzoylamino]-2-hydroxy-butyric Acid

Participants

Reaction Conditions

Reaction Steps

Methyl 2-isocyanato-5-methylthiophene-3-carboxylate (116 mg, 588 μmol, 1.5 eq.) was dissolved in DMF (1000 μL) then combined with 3-amino-4-ethyl-benzoic acid (64.8 mg, 392 μmol, 1.0 eq.) and DIPEA (137 μL, 2.0 eq.). The mixture was heated at 70° C. overnight. The solvent was removed and the product was combined with DMF (500 μL) and HATU (298 mg, 784 μmol, 2.0 eq.). The mixture was stirred at room temperature for 15 minutes before adding (2R,3R)-3-Amino-4-(2-chloro-phenyl)-2-hydroxy-butyric acid ethyl ester (TFA salt, 146 mg, 392 μmol, 1.0 eq.) in DIPEA (137 μL, 2.0 eq.) and DMF (500 μL). The mixture was stirred overnight at room temperature. The solvent was removed and the product was dissolved in THF (600 μL) and 2 M aqueous NaOH (600 μL). The mixture was heated at 80° C. overnight. The product was purified by preparative HPLC to yield the title compound (12.3 mg, 100% purity). MS m/z [M+H]+ calc'd for C26H24ClN3O6S, 542.11. found 542.0.

Provenance & Evidence