反应详情

温度

110 °C

A solution of (S)-ethyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.207 g, 0.460 mmol), 2-(8-fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.151 g, 0.517 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.081 g, 0.070 mmol) in anhydrous DMF (4 mL) was treated with 2.0 M K2CO3 (0.55 mL, 1.100 mmol), degassed by nitrogen stream, then sealed and heated (110° C., microwave) for 60 min. The reaction slurry was filtered though a 0.45 micron syringe tip filter, and the filtrate was purified by biotage silica gel column, eluting with 0%-20% ethyl acetate in hexanes. Individual atropisomers eluted separately, and the early eluting isomer was concentrated under reduced pressure, affording the single isomer, (2S)-ethyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-(8-fluoro-5-methylchroman-6-yl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.095 g, 0.164 mmol, 35.7% yield) as a white glassy solid.

1. customdegassed by nitrogen stream
2. customsealed
3. filtrationThe reaction slurry was filtered though a 0.45 micron syringe tip
4. filtrationfilter
5. customthe filtrate was purified by biotage silica gel column
6. washeluting with 0%-20% ethyl acetate in hexanes
7. washIndividual atropisomers eluted separately
8. washthe early eluting isomer
9. concentrationwas concentrated under reduced pressure