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

A mixture of 118c (80 mg, 0.13 mmol), lithium hydroxide (13 mg, 0.53 mmol), THF (6 mL), i-propanol (4 mL) and water (2 mL) was stirred at room temperature for 0.5 h. The mixture was concentrated under reduced pressure and diluted with water (5 mL). It was then extracted with dichloromethane (2×10 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 118 (20 mg, 26%) as a white solid. MS-ESI: [M+H]+ 558.3. 1H NMR (500 MHz, DMSO-d6) δ 8.56 (d, J=5.0 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 8.10 (s, 1H), 8.05 (d, J=2.5 Hz, 1H), 7.90 (d, J=2.0 Hz, 1H), 7.79-7.76 (m, 1H), 7.50 (d, J=5.0 Hz, 1H), 7.40 (d, J=2.5 Hz, 1H), 5.88 (s, 1H), 4.92 (t, J=5.0 Hz 1H), 4.46-4.45 (m, 2H), 3.91 (q, J=7.5 Hz, 2H), 3.59 (s, 3H), 2.19 (s, 3H), 1.40 (s, 9H), 1.27 (t, J=7.0 Hz, 3H).

1. concentrationThe mixture was concentrated under reduced pressure
2. additiondiluted with water (5 mL)
3. extractionIt was then extracted with dichloromethane (2×10 mL)
4. extractionThe combined dichloromethane extract
5. concentrationwas concentrated under reduced pressure
6. customthe residue was purified with reverse-phase prep-HPLC

ORD 기록

ord-234435d43d1a4b07bda9dcb9712fa99b

출처 데이터셋

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08754077B2