反应详情

A solution of Intermediate 75c (247 mg, 0.31 mmol) and pyridinium p-toluenesulphonate (233 mg, 0.93 mmol) in methanol (14 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 (199.7 mg, 99%). Part of this (50 mg) was further purified by HPLC (XBridge C18 column, 30-90% MeCN in H2O, 0.1% NH4OH) to give the title compound (35 mg). LCMS (Method 5): Rt 4.53 min, m/z 713.4 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.28 (9H, s), 1.57-1.65 (2H, m), 1.68-1.77 (4H, m), 1.80-1.94 (4H, m), 1.97-2.17 (2H, m), 3.07-3.17 (4H, m), 3.48-3.64 (2H, q, J=6.2 Hz), 4.09-4-20 (2H, t, J=6.52 Hz), 4.48-4.58 (1H, t, J=5.7), 4.76-4.84 (1H, m), 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