反应详情

温度

110 °C

To a solution of 3-benzothiazol-2-yl-5-[1-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazol-4-yl]-pyridin-2-ylamine (50.8 mg, 0.122 mmol; 1 eq) and K2CO3 (1.2 mg, 0.0087 mmol, 7 mol %) in toluene (3 mL), ethyl chloroformate (67.0 mg, 0.617 mmol, 5 eq) in toluene (1 mL) was added. The solution was heated to reflux for a total of 10 h (temp=110° C.). The residue was dissolved in water. The aqueous mixture was extracted with CH2Cl2 (3×) and the combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude was purified by column chromatography on silica gel [0.5″×10″ column, eluting with CH2Cl2:EtOAc 1:0→2:1→1:1→1:2→0:1]. Fractions containing product were combined and concentrated in vacuo to give the title compound. MS (ES+): m/z=475.13 (100) [MH+]. HPLC: tR=3.41 min (ZQ2, polar—5 min).

1. temperatureThe solution was heated
2. extractionThe aqueous mixture was extracted with CH2Cl2 (3×)
3. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude was purified by column chromatography on silica gel [0.5″×10″ column
7. washeluting with CH2Cl2:EtOAc 1:0→2:1→1:1→1:2→0:1]
8. additionFractions containing product
9. concentrationconcentrated in vacuo