反应详情

To a stirred mixture of O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.63 g, 1.64 mmol) and aniline (0.14 g, 1.5 mmol) in dichloromethane (10 mL) was added over 5 min the crude solution of 7-cyano-2-(3-methyl[1,2,4]thiadiazol-5-yl)heptanoic acid (2021052) and triethylamine. The resultant reaction mixture was then stirred at room temperature overnight before being quenched with citric acid (5 g) in water (50 mL) and extracted with dichloromethane (3×50 mL). The combined organic fractions were dried (MgSO4) and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (3:1 hexane/ethyl acetate followed by 1:1 hexane/ethyl acetate) to afford 7-cyano-2-(3-methyl[1,2,4]thiadiazol-5-yl)heptanoic acid phenylamide (2021044) (440 mg, 73% over two steps) as a yellow oil.

1. customThe resultant reaction mixture
2. custombefore being quenched with citric acid (5 g) in water (50 mL)
3. extractionextracted with dichloromethane (3×50 mL)
4. dry with materialThe combined organic fractions were dried (MgSO4)
5. customthe solvent was removed under reduced pressure
6. customThe crude product was purified by flash chromatography (3:1 hexane/ethyl acetate followed by 1:1 hexane/ethyl acetate)