反应详情

A 15 mL RBF under nitrogen was charged with 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propan-1-ol (130 mg, 0.24 mmol) in DMA (1.2 mL, 0.24 mmol). To this was added di-tert-butyl diethylphosphoramidite (0.14 mL, 0.57 mmol) and 1-H-tetrazole (1.1 mL, 0.49 mmol). The reaction mixture was stirred at RT for 2 hrs, then cooled to −5° C. and hydrogen peroxide −30 wt. % in water (0.05 mL, 0.51 mmol) added slowly via syringe. The reaction was warmed up to RT and stirred for 2 hrs. The reaction was cooled back to −5° C. and quenched with saturated aqueous solution of sodium thiosulfate. The product was extracted into EtOAc, and the organic layer was collected, dried over sodium sulfate and concentrated to afford a crude yellow residue. The residue was purified by ISCO silica gel chromatography (2-5% MeOH/DCM), and the purified fractions were further purified by Gilson RPLC in system (15%-85% CH3CN/H2O/0.1% TFA) to afford di-tert-butyl 3-(4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylamino)propyl phosphate. MS m/z=734 [M+H]+. Calc'd for C40H44N7O5P: 733.8.

1. temperaturecooled to −5° C.
2. temperatureThe reaction was warmed up to RT
3. stirringstirred for 2 hrs
4. temperatureThe reaction was cooled back to −5° C.
5. customquenched with saturated aqueous solution of sodium thiosulfate
6. extractionThe product was extracted into EtOAc
7. customthe organic layer was collected
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated
10. customto afford a crude yellow residue
11. customThe residue was purified by ISCO silica gel chromatography (2-5% MeOH/DCM)
12. customthe purified fractions were further purified by Gilson RPLC in system (15%-85% CH3CN/H2O/0.1% TFA)