Triphenylphosphine → (2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[1-(3-hydroxypropyl)-1H-pyrazol-3-yl]acrylamide

Participants

Reaction Steps

To a solution of triphenylphosphine (320 mg) in dichloromethane (10 mL) was added N-bromosuccinimide (217 mg) under ice-cooling, followed by stirring for 15 minutes under ice-cooling. A solution of (2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]acrylic acid (200 mg) in dichloromethane (5 mL) was added thereto under ice-cooling, followed by stirring at room temperature for 0.5 hour. A solution of 1-[3-(benzyloxy)propyl]-1H-pyrazol-3-amine (141 mg) in dichloromethane (5 mL) and pyridine (0.09 mL) were added thereto at room temperature, followed by stirring at room temperature overnight. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was sequentially washed with 1 M hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, and dried over anhydrous magnesium sulfate. The crude product obtained by concentration was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1). To a solution of the obtained colorless oily substance in trifluoroacetic acid (5 mL) was added 1,2,3,4,5-pentamethylbenzene (823 mg) at room temperature, followed by stirring at room temperature for 48 hours. To a solution of the oily substance obtained by concentration in methanol (4 mL) was added a 1 M aqueous sodium hydroxide solution (1 mL) at room temperature, followed by stirring at room temperature for 30 minutes. Saturated brine was added thereto, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (hexane:ethyl acetate=2:1, chloroform:methanol=1:0-20:1) to obtain (2E)-3-cyclopentyl-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[1-(3-hydroxypropyl)-1H-pyrazol-3-yl]acrylamide (155 mg) as a white amorphous substance.

Provenance & Evidence