Lithium Hydroxide → 6-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6-oxo-4,7-dihydropyrazolo[1,5-a]pyrazin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 146f (110 mg, 0.172 mmol) in THF/i-propanol/water (4/2/2 mL) was added lithium hydroxide (21 mg, 0.86 mmol). The mixture was stirred at 30° C. for 1 h. After the reaction was complete, the mixture was concentrated under reduced pressure. The residue was diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layer was dried and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 146 as a white solid (45 mg, 44%). MS-ESI: [M+H]+ 599.2. 1H NMR (500 MHz, DMSO-d6) δ 8.57 (d, J=5.0 Hz, 1H), 8.54 (d, J=2.5 Hz, 1H), 8.41 (s, 1H), 8.08 (d, J=2.5 Hz, 1H), 7.91 (d, J=1.5 Hz, 1H), 7.78 (d, J=13.0 Hz, 1H), 7.51 (d, J=5.0 Hz, 1H), 7.42 (d, J=2.5 Hz, 1H), 6.08 (s, 1H), 4.91-4.89 (m, 1H), 4.62 (s, 2H), 4.57 (s, 2H), 4.45-4.43 (m, 2H), 3.61 (s, 3H), 2.98 (s, 3H), 1.40 (s, 9H).

Provenance & Evidence