反应详情

温度

100 °C

A mixture of N-(3-amino-2′-trifluoromethyl-biphenyl-4-yl)-3-(tetrahydro-pyran-4-yl)-acrylamide (76.0 mg, 0.195 mmol, as prepared in the previous step) in toluene (5 mL) was treated with p-toluenesulfonic acid (74.2 mg, 0.390 mmol) and heated to 100° C. under a reflux condenser for 4 h. The cooled mixture was treated with saturated aqueous NaHCO3 (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 24-g Sepra Si 50 SPE column (Isco system: flow rate=20 mL/min; Eluent=1% MeOH—CH2Cl2 for 0-5 min, then 1-4% MeOH—CH2Cl2 for 5-25 min). The resulting residue was purified by RP-HPLC (C18) eluting with CH3CN, 0.1% TFA/water, 10:90 to 50:50, v/v over a period of 20 minutes. The desired column fractions were treated with saturated aqueous NaHCO3 to pH 7 and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated in vacuo to yield (E)-2-[2-(tetrahydro-pyran-4-yl)-vinyl]-5-(2-trifluoromethyl-phenyl)-1H-benzimidazole as a pale yellow solid.

1. extractionextracted with EtOAc (2×50 mL)
2. dry with materialThe combined organic layers were dried over MgSO4
3. concentrationconcentrated in vacuo
4. customThe residue was purified on a 24-g Sepra Si 50 SPE column (Isco system
5. wait1-4% MeOH—CH2Cl2 for 5-25 min)
6. customThe resulting residue was purified by RP-HPLC (C18)
7. washeluting with CH3CN, 0.1% TFA/water, 10:90 to 50:50, v/v over a period of 20 minutes
8. additionThe desired column fractions were treated with saturated aqueous NaHCO3 to pH 7
9. extractionextracted with EtOAc
10. dry with materialThe organic layer was dried over MgSO4
11. concentrationconcentrated in vacuo