反应详情

To a solution of 6-bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1H-benzimidazole (Example 37, 600 mg, 1.57 mmol) in dichloromethane (20 mL) were added diisopropylethylamine (0.82 mL, 4.72 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (0.36 mL, 2.36 mmol) and the resulting mixture was stirred at rt for 16 h. Water was then added and the mixture was extracted with dichloromethane (1×50 mL), dried over Na2SO4, filtered and concentrated to dryness. The residue was then purified with an ISCO CombiFlash Companion using gradient elution from 0% to 30% EtOAc in hexanes to afford the title compound as a white solid (560 mg, 70%, mixture of two regioisomers): Isomer 1 (less polar): 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, 1H), 7.78 (d, 1H), 7.60-7.63 (dd, 1H), 7.31-7.36 (m, 4H), 6.95 (s, 1H), 6.34 (s, 2H), 5.57 (s, 2H), 3.61 (t, 2H), 2.50 (s, 3H), 2.46 (s, 3H), 0.91 (t, 2H), 0.00 (s, 9H); ES-MS m/z 512.21, HPLC RT (Method C) 4.05 min. Isomer 2 (more polar): 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, 1H), 7.79 (d, 1H), 7.59-7.62 (dd, 1H), 7.31-7.34 (m, 4H), 6.94 (s, 1H), 6.35 (s, 2H), 5.57 (s, 2H), 3.61 (t, 2H), 2.50 (s, 3H), 2.47 (s, 3H), 0.92 (t, 2H), 0.00 (s, 9H); ES-MS m/z 512.11, HPLC RT (Method B) 4.03 min.

1. extractionthe mixture was extracted with dichloromethane (1×50 mL)
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated to dryness
5. customThe residue was then purified with an ISCO CombiFlash Companion
6. washelution from 0% to 30% EtOAc in hexanes