Water → HCID 86721457, compound

Participants

Reaction Conditions

Reaction Steps

[step 5] (E)-2-{8-[(7-bromo-2-cyclopropylimidazo[1,2-a]pyridin-3-yl)methyl]-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene}propanenitrile (2.5 g, 4.8 mmol) obtained in step 4 was dissolved in DMF (26 mL), water (6.8 mL), 1,3-bis(diphenylphosphino)propane (0.60 g, 1.5 mmol), potassium carbonate (0.80 g, 5.8 mmol) and palladium acetate (0.33 g, 1.5 mmol) were added. After purging 3 times with carbon monoxide under reduced pressure, the mixture was stirred with heating at 80° C. for 7 hr. The reaction mixture was filtered through celite, activated carbon (0.75 g) was added to the obtained filtrate, and the mixture was stirred with heating at 60° C. for 1.5 hr. The mixture was filtered again through celite, 2 mol/L hydrochloric acid was added to the filtrate, and the mixture was extracted 3 times with a mixed solvent of chloroform-methanol. The combined organic layers were washed 3 times with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue were added isopropylalcohol (25 mL) and ethanol (20 mL), and the mixture was stirred at 80° C. for 1 hr and further at room temperature for 1 hr. The precipitated crystals were collected by suction filtration to give (E)-3-{[11(6H)-(1-cyanoethylidene)-3-fluorodibenzo[b,e]oxepin-8-yl]methyl}-2-cyclopropylimidazo[1,2-a]pyridine-7-carboxylic acid (2.4 g, quantitative).

Provenance & Evidence