Reaction Steps
A solution of 2-[2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-chloro-benzoylamino]-3-(3,4-dichloro-phenyl)-3-oxo-propionic acid methyl ester (35 mg, 0.057 mmol) in THF (2 mL) was cooled to −78° C. and lithium tri-sec-butylborohydride (L-Selectride; 1 M in THF, 86 μL, 0.086 mmol) was added. The mixture was stirred at −78° C. for 1 h and water (0.1 mL), EtOH (0.1 mL), 15% NaOH (0.1 mL), and 30% H2O2 (0.1 mL) were added and the solution was warmed to rt. The mixture was diluted with satd. aq. Na2S2O3 and water and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), and concentrated. The crude product was purified by reverse phase HPLC to provide 2-[2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-chloro-benzoylamino]-3-(3,4-dichloro-phenyl)-3-hydroxy-propionic acid methyl ester as a single diastereomer (20 mg, 57%). The methyl ester was hydrolyzed as in EXAMPLE 2, Part E, to provide the title compound (73%). HPLC: RT=9.51 min. MS (ESI−): mass calcd. for C22H15Cl3N4O5S2, 601.87; m/z found, 599/601 [M−H]−. 1H NMR (400 MHz, CDCl3): 11.31 (s, 1H), 8.34 (dd, J=7.0, 0.6, 1H), 8.19 (dd, J=8.8, 0.6, 1H), 7.71 (dd, J=8.8, 7.1, 1H), 7.64 (d, J=1.9, 1H), 7.43 (d, J=1.7, 1H), 7.36 (d, J=8.3, 1H), 7.23 (d, J=8.5, 1H), 7.18 (dd, J=8.3, 1.8, 1H), 7.01 (d, J=7.3, 1H), 6.86 (dd, J=8.4, 1.9, 1H), 5.37 (d, J=3.7, 1H), 5.10 (dd, J=7.3, 3.9, 1H).
