反应详情

A solution of Intermediate 53c (830 mg, 1.06 mmol) and pyridinium p-toluenesulphonate (799 mg, 3.18 mmol) in methanol (7 mL) was stirred at 40-45° C. for 18.5 h. The cooled mixture was concentrated in vacuo, diluted with sat. sodium hydrogen carbonate solution and extracted with DCM (3×15 mL). The combined organics were dried and concentrated in vacuo. The residue was purified by FCC, using 0-12% MeOH in DCM, to give the product as a solid (613 mg, 83%). An aliquot (50 mg) was further purified by HPLC (XBridge C18 column, 30-90% MeCN in H2O, 0.1% NH4OH) to give the title compound (38 mg). LCMS (Method 5): Rt 4.42 min, m/z 699.5 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.28 (9H, s), 1.57-1.65 (2H, m), 1.68-1.77 (4H, m), 1.80-1.97 (2H, m), 1.98-2.17 (2H, m), 3.11-3.17 (4H, m), 3.74 (2H, q, J=5.0 Hz), 4.12 (2H, t, J=5.0 Hz), 4.76-4.85 (1H, m), 4.90 (1H, t, J=5.1 Hz), 5.54 (1H, t, J=4.3 Hz), 6.34 (1H, s), 7.05-7.11 (2H, m), 7.16 (1H, dd, J=2.0, 9.9 Hz), 7.21-7.41 (5H, m), 7.54 (1H, d, J=8.5 Hz), 7.59-7.65 (2H, m), 8.14 (1H, br s).

1. concentrationThe cooled mixture was concentrated in vacuo
2. additiondiluted with sat. sodium hydrogen carbonate solution
3. extractionextracted with DCM (3×15 mL)
4. customThe combined organics were dried
5. concentrationconcentrated in vacuo
6. customThe residue was purified by FCC