反应详情

温度

25 °C

In a round bottom flask was placed (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4-difluoro-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (70 mg, 0.13 mmol), methanol (3 mL) and p-toluenesulfonic acid (5 mg, 0.15 mmol). The mixture was stirred at 25° C. for 24 h and then concentrated in vacuo and dissolved in ethyl acetate and concentrated in vacuo with silica gel (1 g). Purification by Biotage flash chromatography (AnaLogix SF15-12 g column, 100% ethyl acetate to 10% methanol/ethyl acetate) afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4-difluoro-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (52 mg, 82%) as a white foam: HR-ES-MS m/z calculated for C21H23N4O5ClF2 [M+H]+ 485.1398, observed 485.1396; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.66 (t, J=19.3 Hz, 3H), 3.21-3.33 (m, 2H), 3.69-3.81 (m, 1H), 3.87 (dd, J=13.6, 7.5 Hz, 1H), 4.01-4.17 (m, 1H), 4.30 (d, J=18.4 Hz, 1H), 4.47 (d, J=18.4 Hz, 1H), 4.72 (t, J=5.6 Hz, 1H), 4.81 (s, 1H), 4.95 (d, J=5.1 Hz, 1H), 5.12 (dd, J=9.1, 5.1 Hz, 1H), 6.42 (d, J=2.1 Hz, 1H), 7.32-7.41 (m, 1H), 7.42-7.53 (m, 2H), 7.55 (dd, J=2.1 Hz, 1H), 7.66 (d, J=7.8 Hz, 1H), 10.85 (s, 1H).

1. customIn a round bottom flask was placed
2. concentrationconcentrated in vacuo
3. dissolutiondissolved in ethyl acetate
4. concentrationconcentrated in vacuo with silica gel (1 g)
5. customPurification by Biotage flash chromatography (AnaLogix SF15-12 g column, 100% ethyl acetate to 10% methanol/ethyl acetate)