反应详情

温度

130 °C

To a solution of 5-bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole (94.0 mg, 0.257 mmol) in 4:1 dioxane:water (3.0 mL) was added 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (57 mg, 0.27 mmol), cesium carbonate (251 mg, 0.771 mmol), and tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.026 mmol). The solution was degassed with argon and heated in a microwave reactor at 130° C. for 105 minutes. The reaction was concentrated in vacuo and the residue taken up in DCM (25 mL) and water (10 mL). The layers were separated and the aqueous layer was extracted with DCM (2×10 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→80/20) followed by HPLC purification (formic acid method) to give 26 mg of the title compound as a yellow solid (29% yield). LC/MS (FA) ES+ 352. 1H NMR (300 MHz, d4-MeOH) δ: 8.62-8.60 (m, 2H), 7.90-7.88 (m, 2H), 7.66-7.55 (m, 1H), 7.26-7.24 (m, 2H), 7.20-7.17 (m, 2H), 6.92 (dd, 1H, J=2.7, 1.5 Hz), 6.32 (dd, 1H, J=3.5, 1.5 Hz), 6.21 (dd, 1H, J=3.5, 2.7 Hz), 4.28 (s, 2H).

1. customThe solution was degassed with argon
2. concentrationThe reaction was concentrated in vacuo
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with DCM (2×10 mL)
5. dry with materialThe combined organic layers were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→80/20)
9. customfollowed by HPLC purification (formic acid method)