反应详情

To a solution of 2-[5-(4,5-diamino-2-fluoro-3-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol (7.220 g, 21.72 mmol) and 1-ethyl-3-(N-(ethylcarbamoyl)-C-methylsulfanyl-carbonimidoyl)urea (6.054 g, 26.06 mmol, CB Research and Development) in 1,4-dioxane (36.1 mL, Sigma-Aldrich 360481) was added a pH 3.5 buffer (72.2 mL), prepared by dissolving NaOAc trihydrate (5.32 g) in 1N aqueous H2SO4 (37 mL). The reaction mixture was stirred at reflux overnight (HPLC showed complete conversion), cooled to room temperature, and poured portion-wise (frothing) into a stirring solution of aqueous saturated NaHCO3 (144 mL) giving pH 8-9. This was stirred for 20 minutes, the solid was collected by filtration, washed copiously with water to neutral pH, and then more sparingly with EtOH. The solid was dried under reduced pressure giving a beige solid (7.90 g, 99% HPLC purity). LCMS (C18 column eluting with 10-90% CH3CN/water gradient over 5 minutes with formic acid modifier) M+1: 429.45 (2.03 min). HPLC retention time was 3.89 min (YMC ODS-AQ 150×3.0 mm column eluting with 10-90% CH3CN/water gradient over 8 minutes with 0.1% TFA modifier and 1 mL/min flow rate).

1. customprepared
2. temperatureat reflux overnight (HPLC showed complete conversion)
3. customgiving pH 8-9
4. stirringThis was stirred for 20 minutes
5. filtrationthe solid was collected by filtration
6. washwashed copiously with water to neutral pH
7. customThe solid was dried under reduced pressure
8. customgiving a beige solid (7.90 g, 99% HPLC purity)
9. washLCMS (C18 column eluting with 10-90% CH3CN/water gradient over 5 minutes with formic acid modifier) M+1: 429.45 (2.03 min)
10. washHPLC retention time was 3.89 min (YMC ODS-AQ 150×3.0 mm column eluting with 10-90% CH3CN/water gradient over 8 minutes with 0.1% TFA modifier and 1 mL/min flow rate)