Propionyl chloride → (S)-5-[3-(5-ethyl-1,2,4-oxadiazol-3-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one

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Reaction Conditions

Reaction Steps

(S)-5-(3-Cyanophenyl)-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one (300 mg, 0.854 mmol) obtained in Step 1 was dissolved in ethanol (10 mL), and the mixture was stirred at 70° C. for 3 hours after adding hydroxylamine hydrochloride (65.0 mg, 0.939 mmol) and N,N-diisopropylethylamine (0.164 mL, 0.939 mmol). The mixture was concentrated, diluted with chloroform, and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in pyridine (4 mL), and stirred therein at 90° C. for 5 hours after adding propionyl chloride (0.103 mL, 1.19 mmol). The mixture was cooled to room temperature, and diluted with ethyl acetate. The organic layer was washed with 1 mol/L hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was then purified by silica gel column chromatography to give (S)-5-[3-(5-ethyl-1,2,4-oxadiazol-3-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one (252 mg, 70%).

Provenance & Evidence