反应详情

温度

97.5 °C

A solution of 1-(5-bromo-6-fluoro-benzothiazol-2-yl)-3-ethyl-urea (0.05 g, 0.15 mmol), tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperazine-1-carboxylate (0.12 g, 0.31 mmol) and K3PO4 (0.13 g, 0.61 mmol) in DMF-H2O (5.0 mL, 3:2) was degassed by flushing with nitrogen for 15 min. Dichlorobis(triphenylphosphine)-palladium(II) (0.021 g, 0.03 mmol) was then added to the reaction mixture followed by degassing with nitrogen for another 15 min. The resulting reaction mixture was then heated to 95-100° C. for 2 h. After the completion of the reaction (TLC monitoring), the reaction mixture was cooled to room temperature and poured onto ice-cold water followed by extraction with EtOAc (2×50 mL). The combined organics was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude was then purified over silica gel (100-200 M, 1.60% MeOH-DCM) to obtain the desired product (0.015 g, 20%). 1H-NMR (400 MHz, DMSO-d6): δ 1.08 (t, J=7.20 Hz, 3H), 1.43 (s, 9H), 3.20 (m, 2H), 3.42 (br s, 4H), 3.79 (br s, 4H), 6.71 (br s, 1H), 7.76 (d, J=6.80 Hz, 1H), 7.92 (d, J=10.40 Hz, 1H), 8.62 (s, 2H) and 10.74 (br s, 1H). MS: 502.27 (M+H)+. Qualitative HPLC Purity (Acquity BEH C-18, 100×2.1 mm, 272 nm): 99.21% (Rt=6.51 min).

1. customby flushing with nitrogen for 15 min
2. customby degassing with nitrogen for another 15 min
3. customThe resulting reaction mixture
4. customAfter the completion of the reaction (TLC monitoring)
5. temperaturethe reaction mixture was cooled to room temperature
6. additionpoured onto ice-cold water
7. extractionfollowed by extraction with EtOAc (2×50 mL)
8. washThe combined organics was washed with brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe crude was then purified over silica gel (100-200 M, 1.60% MeOH-DCM)