反应详情

温度

55 °C

NCS (75.43 mg, 0.5649 mmol) was added to a solution of tert-butyl N-[[4-[(E)-hydroxyiminomethyl]phenyl]methyl]-N-methyl-carbamate (129.4 mg, 0.4896 mmol) in DMF (571.5 μL) and the reaction mixture heated at 55° C. for 15 min. After the reaction mixture was allowed to cool to room temperature, 5-(4-isopropylsulfonylphenyl)-3-vinyl-pyrazin-2-amine (114.3 mg, 0.3766 mmol) was added followed by the dropwsie addition of Et3N (76.22 mg, 105.0 μL, 0.7532 mmol). The reaction mixture was stirred at rt for 45 mins followed by heating to 65° C. for 1 hour. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (5 mL) and water (5 mL) and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×5 mL) and the combined organic extracts washed with water (3×10 mL), dried over MgSO4, and concentrated in vacuo to a solid. The residue was purified by column chromatography on silica using with 0-100% Ethylacetate/petroleum ether as elaunt to yield tert-butyl 4-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzyl(methyl)carbamate. LC/MS m/z 510.1 [M+1-56]+.

1. temperatureto cool to room temperature
2. temperatureby heating to 65° C. for 1 hour
3. temperatureThe reaction mixture was cooled to room temperature
4. customthe layers separated
5. extractionThe aqueous layer was extracted further with ethyl acetate (2×5 mL)
6. washthe combined organic extracts washed with water (3×10 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo to a solid
9. customThe residue was purified by column chromatography on silica using with 0-100% Ethylacetate/petroleum ether as elaunt