Reaction Steps
In a round bottom flask was placed (S)-4-(t-butyl-dimethyl-silanyloxy)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-butyramide (128 mg, 0.21 mmol), methanol (5 mL) and p-toluenesulfonic acid monohydrate (10 mg) and stirred at 25° C. for 16 h. The mixture was then concentrated and treated with ethyl acetate and methanol to solubilize the material and concentrated in vacuo with silica gel (1 g). Purification by Biotage flash chromatography (AnaLogix, 25 g column, 100% ethyl acetate to 20% methanol/ethyl acetate) afforded material that was not pure. A second purification by Biotage flash chromatography (AnaLogix, 25 g column, 100% ethyl acetate to 20% methanol/ethyl acetate) afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4-hydroxy-butyramide (43 mg, 45%) as a white foam: HR-ES-MS m/z calculated for C20H23N4O6Cl [M+H]+ 451.1379, observed 451.1379; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.88-2.06 (m, 2H), 3.23-3.31 (m, 2H), 3.37-3.50 (m, 2H), 3.72-3.81 (m, 1H), 3.86 (dd, J=13.9, 7.9 Hz, 1H), 4.09 (dd, J=13.5, 3.9 Hz, 1H), 4.29 (d, J=18.3 Hz, 1H), 4.50-4.60 (m, 2H), 4.71 (t, J=5.6 Hz, 1H), 4.80 (s, 1H), 4.84 (dd, J=8.4, 5.4 Hz, 1H), 4.94 (d, J=5.3 Hz, 1H), 6.41 (d, J=2.1 Hz, 1H), 7.11 (d, J=7.9 Hz, 1H), 7.34-7.41 (m, 1H), 7.43-7.57 (m, 2H), 7.66 (dd, J=8.0, 1.2 Hz, 1H), 10.59 (s, 1H).
