反应详情

To a solution of (3-{(S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-yl)-acetic acid ethyl ester (prepared as in Example 148, 0.130 g, 0.26 mmol) in tetrahydrofuran (5 mL) was added an aqueous lithium hydroxide solution (0.5N, 2 mL). The resulting mixture was stirred at room temperature for 3 h. The solvents were evaporated and the residue neutralized with 1N aqueous hydrochloric acid, extracted with ethyl acetate. The combined organic layers were washed with water, saturated sodium chloride solution and dried over sodium sulfate. The mixture was filtered and evaporated which afforded (3-{(S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoylamino}-pyrazol-1-yl)-acetic acid (0.118 g, 96%) as a white solid: HR-ES-MS m/z calculated for C24H27FN4O5 [M+H]+ 471.2038 observed 471.2036; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.72-0.81 (m, 2H), 0.90 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 0.97-1.06 (m, 2H), 1.37-1.51 (m, 1H), 1.52-1.65 (m, 1H), 1.65-1.82 (m, 1H), 2.00-2.15 (m, 1H), 4.21 (d, J=18.4 Hz, 1H), 4.59 (d, J=18.4 Hz, 1H), 4.62 (s, 2H), 4.86 (s, 1H), 4.85-4.93 (m, 1H), 6.42 (d, J=2.0 Hz, 1H), 6.94 (t, J=6.9 Hz, 1H), 7.15 (t, J=7.8 Hz, 1H), 7.21-7.31 (m, 1H), 7.54 (d, J=2.0 Hz, 1H), 10.75 (s, 1H).

1. customThe solvents were evaporated
2. extractionextracted with ethyl acetate
3. washThe combined organic layers were washed with water, saturated sodium chloride solution
4. dry with materialdried over sodium sulfate
5. filtrationThe mixture was filtered
6. customevaporated which