Water → 6-Tert-butyl-2-[4-[5-[(5-ethyl-1-methyl-pyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

Participants

Reaction Steps

To a solution of 122c (150 mg, 0.25 mmol) in THF/i-propanol/water (2.5/1/0.5 mL) was added lithium hydroxide (70 mg, 2.5 mmol) at 35° C. After the reaction was stirred for 3 h, LCMS indicated the reaction was completed. The mixture was poured into water (15 mL) and extracted with dichloromethane (3×20 mL). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue solid was purified by reverse-phase prep-HPLC to afford 122 (49 mg, 35%) as a white solid. MS-ESI: [M+H]+ 557.8. 1H NMR (500 MHz, CDCl3) δ 8.59 (d, J=5.0 Hz, 1H), 8.51 (d, J=2.5 Hz, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.88 (d, J=1.5 Hz, 1H), 7.73 (m, 1H), 7.64 (d, J=5.0 Hz, 1H), 7.41 (d, J=1.5 Hz, 1H), 5.92 (s, 1H), 4.59 (s, 2H), 3.72 (s, 3H), 3.68 (s, 3H), 2.64 (m, 2H), 1.47 (s, 9H), 1.27 (t, J=2.5, 3H)

Provenance & Evidence