Cesium carbonate → (S)-3-(6-chloro-4-oxochroman-7-ylamino)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one

(S)-3-Amino-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (Example 34, Steps A-D; 120 mg, 0.42 mmol) was dissolved in toluene (3 mL). 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (26 mg, 0.042 mmol), 6-chloro-4-oxochroman-7-yl trifluoromethanesulfonate (206 mg, 0.62 mmol) and Cs2CO3 (162 mg, 0.498 mmol) were added and the reaction was bubbled through with nitrogen for 5 minutes. Pd2 dba3 (19.0 mg, 0.021 mmol) was added and the reaction plunged into 95° C. oil bath overnight. The reaction was cooled to ambient temperature, partitioned between water and EtOAc, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (75 to 100% EtOAc in hexanes) to afford a mixture. The mixture was further purified by reverse phase chromatography (25 to 95% ACN in water) to afford (S)-3-(6-chloro-4-oxochroman-7-ylamino)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (10 mg, 0.022 mmol, 5% yield. Mass spectrum (apci) m/z=470.3 (M+H).

1. customthe reaction was bubbled through with nitrogen for 5 minutes
2. customplunged into 95° C.
3. customovernight
4. custompartitioned between water and EtOAc
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified over silica gel (75 to 100% EtOAc in hexanes)
9. customto afford a mixture
10. customThe mixture was further purified by reverse phase chromatography (25 to 95% ACN in water)

ORD 기록

ord-865030744fae48ef8b0099d7e35502c8

출처 데이터셋

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08754226B2