Hydrochloric Acid → HCID 57920068, compound

Participants

Reaction Steps

A solution of (S)-2-[4-(3-ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-amide (prepared in Example 152, 0.251 g, 0.46 mmol) in tetrahydrofuran (25 mL) was treated with 1N aqueous hydrochloric acid (10 mL). The reaction mixture was stirred for 20 h at room temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, a saturated sodium chloride solution and dried over magnesium sulfate. The mixture was filtered and evaporated and the residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 10% to 100% (9:1 dichloromethane:methanol)/hexanes) to afford (S)-2-[4-(3-ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amide (0.210 g, 90%) as a fluffy white solid: HR-ES-MS m/z calculated for C24H28F2N4O6, [M+H]+ 507.2050 observed 507.2051; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.92 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.9 Hz, 3H), 1.35 (t, J=6.9 Hz, 3H), 1.40-1.56 (m, 1H), 1.56-1.73 (m, 1H), 1.75-1.93 (m, 1H), 3.42-3.62 (m, 1H), 3.61-3.74 (m, 1H), 4.13 (q, J=6.9 Hz, 2H), 4.31 (d, J=18.7 Hz, 1H), 4.51-4.69 (m, 2H), 4.73 (t, J=5.7 Hz, 1H). 5.02 (dd, J=10.6, 4.2 Hz, 1H), 5.08 (s, 1H), 5.55 (d, J=5.1 Hz, 1H), 7.12-7.23 (m, 1H), 7.23-7.33 (m, 1H), 8.45 (s, 1H), 9.17 (s, 1H), 11.16 (s, 1H).

Provenance & Evidence