作为医药中间体,用于相关药物分子的合成研究(具体用途需结合参考文献进一步验证)。
医药
合成路线1
- 原料: 5-碘-2'-脱氧尿苷(5.0g,14mmol)、咪唑(1.09g,16mmol)、叔丁基二甲基氯硅烷(TBDMSCl,2.41g,16mmol)
- 溶剂: 无水N,N-二甲基甲酰胺(DMF,70mL)
- 步骤: 向5-碘-2'-脱氧尿苷的DMF溶液中加入咪唑,0℃下加入TBDMSCl;冰浴搅拌过夜
- 淬灭与分离: 用饱和NaHCO₃水溶液淬灭反应,NaCl水溶液洗涤,乙酸乙酯(EtOAc)萃取
- 干燥与纯化: 有机层经MgSO₄干燥,减压浓缩后,硅胶柱色谱纯化(洗脱剂:EtOAc/石油醚=3:7,v/v)
- 收率: 90%(得到5.9g无色固体产物)
- 表征数据: ¹H NMR (d6-DMSO) δ: 0.00 (s, 3H, CH₃), 0.79 (s, 9H, tBu), 1.88-1.97 (m, 1H, H-2'), 2.00-2.05 (m, 1H, H-2'), 3.59-3.71 (m, 2H, H-5'), 3.75 (br s, 1H, H-4'), 4.06 (br s, 1H, H-3'), 5.18 (d, J=4.0Hz, 1H, OH), 5.98 (t, J=5.9Hz, 1H, H-1'), 7.89 (s, 1H, H-6), 11.62 (s, 1H, NH);质谱(-ve电喷雾)计算值C₁₅H₂₅IN₂O₅Si [M-H]⁻ 468.06,实测值467
- 参考文献: [1] EP2607369 (2015, B1); [2] Journal of Medicinal Chemistry (2004, 47(7), 1840-1846); [3] WO2017/58953 (2017, A1); [4] European Journal of Medicinal Chemistry (2015, 101, 668-680); [5] European Journal of Medicinal Chemistry (2016, 120, 304-312); [6] WO2017/53834 (2017, A1); [7] Journal of the Chemical Society, Perkin Transactions 1 (1992, 19, 2537-2544); [8] Journal of Heterocyclic Chemistry (1991, 28(3), 711-715); [9] Bioorganic and Medicinal Chemistry Letters (2017, 27(4), 897-900); [10] WO2017/185026 (2017, A1); [11] Chemical Communications (1997, 19, 1871-1872); [12] Journal of Labelled Compounds and Radiopharmaceuticals (2014, 57(8), 540-549)