Cesium carbonate → 2-((2S)-4-methyl-1-(5-methyl-5H-chromeno[3,4-c]pyridin-8-yloxy)pentan-2-yl)isoindoline-1,3-dione

온도

80 °C

To a stirred solution of 8-bromo-5-methyl-5H-chromeno[3,4-c]pyridine (200 mg, 0.724 mmol) in toluene (4 mL), were added (S)-2-(1-hydroxy-4-methylpentan-2-yl)isoindoline-1,3-dione (537 mg, 2.173 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (185 mg, 0.435 mmol), cesium carbonate (354 mg, 1.086 mmol) and palladium (II) acetate (48.8 mg, 0.217 mmol). Nitrogen was bubbled through the reaction mixture for 10 min and the mixture was heated at 80° C. 12 h. The reaction mixture was cooled to room temperature and filtered through celite and residue rinsed with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via prep TLC (60% ethyl acetate in pet ether) to afford 2-((2S)-4-methyl-1-(5-methyl-5H-chromeno[3,4-c]pyridin-8-yloxy)pentan-2-yl)isoindoline-1,3-dione (205 mg, 0.463 mmol, 64% yield). LCMS (ESI) m/e 443.2 [(M+H)+, calcd for C27H27N2O4 443.2]; LC/MS retention time (Method C): tR=2.27 min.

1. customNitrogen was bubbled through the reaction mixture for 10 min
2. custom12 h
3. temperatureThe reaction mixture was cooled to room temperature
4. filtrationfiltered through celite and residue
5. washrinsed with ethyl acetate
6. concentrationThe filtrate was concentrated under reduced pressure
7. custompurified via prep TLC (60% ethyl acetate in pet ether)

ORD 기록

ord-350e0e34f4e54b4dba955127c82e9d75

출처 데이터셋

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08969564B2