1,4-Dibromobutane → 8-(4-fluorophenyl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro-4H-1,3,3a,8-tetraazaazulene

Participants

Reaction Steps

60% sodium hydride (10 mg) was added to a solution of (4-fluorophenyl)-{5-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-4H-[1,2,4]triazol-3-yl}amine synthesized in Example 162 (47.5 mg) in DMF (3 mL) at room temperature, and the reaction solution was stirred at room temperature for 10 minutes. 1,4-Dibromobutane (0.02 mL) was added to the reaction solution at room temperature, and the reaction solution was stirred at room temperature for two hours. 60% sodium hydride (5 mg) was added to the reaction solution at room temperature, and the reaction solution was stirred at room temperature for two hours. A saturated ammonium chloride solution was added to the reaction solution at 0° C., followed by extraction with ethyl acetate. The resulting extract was washed with a saturated sodium bicarbonate solution and a saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system, then ethyl acetate-methanol system), silica gel column chromatography (elution solvent: heptane-ethyl acetate system, then ethyl acetate-methanol system) and CHIRALPAK™ IA manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: ethanol) to obtain 14 mg of the title compound. The property values of the compound are as follows.

Provenance & Evidence