反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 0 °C
PROCEDURE
实验过程
60% Sodium hydride in mineral oil (0.470 g, 11.75 mmol) was added to (S)-3-hydroxydihydrofuran-2(3H)-one (0.764 mL, 9.80 mmol) in anhydrous THF (30 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (CAS no. 52079-23-9) (2.87 g, 10.77 mmol) was added portionwise maintaining the temperature below 5° C. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was neutralised with 1M citric acid and the majority of the THF removed in vacuo. The reaction mixture diluted with water (20 mL) and ethyl acetate (50 mL). The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (2×100 mL). The combined organics were washed with saturated brine (75 mL), water (75 mL) dried (MgSO4), filtered and evaporated. The residue was purified by flash silica chromatography, eluting with 50 to 100% ethyl acetate in isohexane to afford the product (1.970 g, 61%). 1H NMR (400 MHz, CDCl3) 2.52-2.62 (1H, m), 2.92-3.00 (1H, m), 4.41-4.47 (1H, m), 4.59-4.64 (1H, m), 6.11-6.16 (1H, m), 7.46-7.49 (1H, m), 8.00-8.02 (1H, m), 8.37 (1H, s), 8.61-8.63 (1H, m), 8.64 (1H, s); m/z (ESI+) (M+H)+=332; HPLC tR=1.51 min.
WORKUP
后处理
- addition52079-23-9) (2.87 g, 10.77 mmol) was added portionwise
- temperaturemaintaining the temperature below 5° C
- temperatureto warm to room temperature
- stirringstirred for 1 hour
- customthe majority of the THF removed in vacuo
- additionThe reaction mixture diluted with water (20 mL) and ethyl acetate (50 mL)
- customThe organic layer was separated
- extractionthe aqueous layer re-extracted with ethyl acetate (2×100 mL)
- washThe combined organics were washed with saturated brine (75 mL), water (75 mL)
- dry with materialdried (MgSO4)
- filtrationfiltered
- customevaporated
- customThe residue was purified by flash silica chromatography
- washeluting with 50 to 100% ethyl acetate in isohexane