2,6-Lutidine → HCID 86721354, compound

Participants

Reaction Steps

[step 1] (E)-2-(3-fluoro-8-{[4-hydroxy-2-(hydroxymethyl)-1H-benzo[d]imidazol-1-yl]methyl}dibenzo[b,e]oxepin-11(6H)-ylidene)propanenitrile (245 mg, 0.56 mmol) obtained in Reference Example 2A, step 4 was dissolved in dichloromethane (2.8 mL), 2,6-lutidine (0.22 mL, 1.89 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate (0.38 mL, 1.67 mmol) were added under ice-cooling, and the mixture was stirred at room temperature for 1 hr. To the mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted 3 times with chloroform. The combined organic layers were washed with 1 mol/L hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was dissolved in methanol (2.8 mL), potassium carbonate (384 mg, 2.77 mmol) was added, and the mixture was stirred at room temperature for 13 hr. Water was added to the mixture, and the mixture was extracted 3 times with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-85/15 v/v) to give (E)-2-[8-({2-[(tert-butyldimethylsiloxy)methyl]-4-hydroxy-1H-benzo[d]imidazol-1-yl}methyl)-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrile (203 mg, 66%).

Provenance & Evidence