反应详情

diethylcyanophosphonate (41.07 mg, 37.64 μL, 0.2518 mmol) was added to a solution of tert-butyl 3-[4-[5-amino-6-(hydrazinecarbonyl)pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate (100 mg, 0.2098 mmol), 4-(4-tert-butoxycarbonylmorpholin-3-yl)benzoic acid (64.48 mg, 0.2098 mmol) and Et3N (25.48 mg, 35.10 μL, 0.2518 mmol) in DMF (1.500 mL) and the resulting solution stirred at ambient temperature for 20 minutes. A further portion of diethylcyanophosphonate (68.44 mg, 62.73 μL, 0.4196 mmol) and Et3N (42.46 mg, 58.48 μL, 0.4196 mmol) were added and the reaction mixture stirred at 55° C. for 20 hours. Further portions of Et3N (42.46 mg, 58.48 μL, 0.4196 mmol) and diethylcyanophosphonate (68.44 mg, 62.73 μL, 0.4196 mmol) were added and the reaction mixture stirred at 55° C. for a further 3 hours. Further portions of Et3N (42.46 mg, 58.48 μL, 0.4196 mmol) and diethylcyanophosphonate (68.44 mg, 62.73 μL, 0.4196 mmol) were added and the reaction mixture stirred at 55° C. for a further 4.5 hours. The reaction mixture was cooled to ambient temperature and diluted with water and ethyl acetate and the layers separated. The aqueous layer was extracted further with ethyl acetate (×2) and the combined organic extracts were washed with water (×2), brine (×2), dried over MgSO4, and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 80% EtOAc/Petroleum Ether, loaded in DCM) to give the sub-title product as a yellow solid (81 mg, 51% Yield). LC/MS m/z 748.1 [M+1]+.

1. stirringthe reaction mixture stirred at 55° C. for 20 hours
2. stirringthe reaction mixture stirred at 55° C. for a further 3 hours
3. stirringthe reaction mixture stirred at 55° C. for a further 4.5 hours
4. temperatureThe reaction mixture was cooled to ambient temperature
5. customthe layers separated
6. extractionThe aqueous layer was extracted further with ethyl acetate (×2)
7. washthe combined organic extracts were washed with water (×2), brine (×2)
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 80% EtOAc/Petroleum Ether, loaded in DCM)