Lithium Hydroxide → 2-((1R,3S)-3-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)cyclohexylamino)oxazole-4-carboxylic acid

To a solution of methyl 2-[[(1R,3S)-3-[[5-fluoro-2-[5-fluoro-1-(p-tolylsulfonyl)-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-4-yl]amino]cyclohexyl]-amino]oxazole-4-carboxylate, 71a, (0.028 g, 0.045 mmol) in THF (1 mL) was added LiOH (1 mL of 1 M solution, 1.000 mmol) and the reaction mixture was warmed to 130° C. via microwave irradiation. After heating and stirring for 20 minutes, the mixture was cooled to room temperature. All volatiles were removed under a stream of nitrogen and heat. The crude residue was suspended in MeOH and a few drops of trifluoroacetic acid were added to protonate molecule (solution occurs). The mixture was filtered and purified by reverse phase HPLC (5-95% CH3CN/H2O) to afford 5 mg of the desired product as a TFA salt: 1H NMR (300 MHz, MeOD) δ 8.83 (s, 1H), 8.67-8.09 (m, 4H), 2.67 (s, 3H), 2.18 (m, 5H), 1.34 (d, J=29.6 Hz, 3H); LCMS RT=1.78 (M+1) 456.07.

1. temperatureAfter heating
2. temperaturethe mixture was cooled to room temperature
3. customAll volatiles were removed under a stream of nitrogen
4. temperatureheat
5. additiona few drops of trifluoroacetic acid were added to protonate molecule (solution occurs)
6. filtrationThe mixture was filtered
7. custompurified by reverse phase HPLC (5-95% CH3CN/H2O)

ORD 기록

ord-a5de0b3cf77b45c4942beb8c93d6b62b

출처 데이터셋

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09345708B2