反应详情

A solution of (S)-2-{4-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid pyrazin-2-ylamide (0.025, 0.05 mmol) in tetrahydrofuran (5 mL) was treated with 1 M hydrochloric acid (1 mL) and stirred at room temperature overnight. The resulting mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous phase made basic (pH=8) by the addition of a 1N aqueous sodium hydroxide and extracted with ethyl acetate. The combined organic layers were concentrated in vacuo and the residue purified by flash column chromatography (silica gel 0% to 20% tetrahydrofuran/ethyl acetate) to afford (S)-2-{4-[4-((S)-2,3-dihydroxy-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid pyrazin-2-ylamide (15 mg, 65%) as a white solid: HR-ES-MS m/z calculated for C23H28N4O5 [M+H]+ 441.2133, observed 441.2132; 1H NMR (300 MHz, CDCl3) δ ppm 1.05 (d, J=6.4 Hz, 3H), 1.10 (d, J=6.4 Hz, 3H), 1.43-1.82 (m, 2H), 1.85-2.00 (m, 1H), 2.62 (dd, J=13.0, 11.2 Hz, 1H), 2.85 (d, J=13.9 Hz, 1H), 3.35 (br. s., 2H), 3.61-3.84 (m, 2H), 3.94-4.16 (m, 2H), 4.31 (d, J=18.1 Hz, 1H), 4.78-4.87 (m, 1H), 4.87 (br. s., 1H), 7.01 (d, J=8.2 Hz, 2H), 7.24-7.27 (m, 2H), 8.26 (s, 1H), 8.38 (s, 1H), 9.62 (s, 1H), 10.27 (br. s., 1H).

1. customThe resulting mixture was partitioned between ethyl acetate and water
2. customThe layers were separated
3. additionby the addition of a 1N aqueous sodium hydroxide
4. extractionextracted with ethyl acetate
5. concentrationThe combined organic layers were concentrated in vacuo
6. customthe residue purified by flash column chromatography (silica gel 0% to 20% tetrahydrofuran/ethyl acetate)