作为医药中间体或活性成分,用于相关药物研发与生产。
医药
合成路线 1(1. 合成:56059-30-4)
产率:60%
合成条件:Stage #1: With potassium hydroxide In water at 100℃; for 1.33 h; Stage #2: at 60℃; for 6 h;
实验步骤:FUAC的编写方法已在文献[21]中公布,并作了一些修改。 将KOH(0.60g,10.6mmol,10mL)的水溶液加入到5-FU(1g,5.2mmol)中。 将反应混合物在100℃下搅拌80分钟。 然后在60℃的油浴中逐渐加入氯乙酸(84mL,0.5g,5.2mmol)溶液并搅拌6小时。 通过加入稀释的HCl以达到pH = 2并冷却至4℃12小时酸化结果。 通过过滤收集形成的沉淀,并将其溶解在饱和KHCO 3溶液中。 再次,将溶液用稀HCl酸化至pH = 2,得到FUAC的针状晶体(0.82g,60%收率)。
参考文献:
- [1] Chemical Communications, 2011, vol. 47, # 38, p. 10713 - 10715 [2] Medicinal Chemistry Research, 2007, vol. 16, # 7-9, p. 370 - 379 [3] Nucleosides, Nucleotides and Nucleic Acids, 2011, vol. 30, # 4, p. 280 - 292 [4] Chemical Communications, 2016, vol. 52, # 30, p. 5254 - 5257 [5] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 11, p. 2584 - 2588 [6] Chemistry - A European Journal, 2013, vol. 19, # 38, p. 12806 - 12814 [7] Molecules, 2017, vol. 22, # 11, [8] Carbohydrate Polymers, 2017, vol. 157, p. 1442 - 1450 [9] Patent: WO2017/89800, 2017, A1. Location in patent: Page/Page column 37; 39 [10] Patent: US2008/4237, 2008, A1. Location in patent: Page/Page column 5; 9 [11] Patent: US2008/85871, 2008, A1. Location in patent: Page/Page column 6-7 [12] Chemistry of Natural Compounds, 1994, vol. 30, # 5, p. 607 - 612 [13] Khimiya Prirodnykh Soedinenii, 1994, # 5, p. 655 - 662 [14] Bulletin des Societes Chimiques Belges, 1995, vol. 104, # 3, p. 129 - 136 [15] Pharmazie, 2006, vol. 61, # 5, p. 489 - 490 [16] Molecules, 2010, vol. 15, # 4, p. 2114 - 2123 [17] Journal of the Brazilian Chemical Society, 2011, vol. 22, # 2, p. 308 - 318 [18] Natural Product Research, 2011, vol. 25, # 19, p. 1817 - 1826 [19] International Journal of Pharmaceutics, 2010, vol. 388, # 1-2, p. 95 - 100 [20] European Journal of Medicinal Chemistry, 2012, vol. 49, p. 48 - 54 [21] Chinese Chemical Letters, 2012, vol. 23, # 6, p. 677 - 680 [22] Carbohydrate Polymers, 2012, vol. 87, # 4, p. 2642 - 2647,6 [23] Patent: US2014/155577, 2014, A1. Location in patent: Paragraph 0189 [24] Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 2016, vol. 46, # 5, p. 653 - 658 [25] Patent: CN107892686, 2018, A. Location in patent: Paragraph 0031-0034
合成路线 2(2. 合成:56059-30-4)
产率:85%
合成条件:Stage #1: With potassium hydroxide In water at 40 - 60℃; for 5 h; Stage #2: With hydrogenchloride In waterCooling with ice
实验步骤:将KOH(2.56g,45mmol)和5-氟尿嘧啶(1.34g,10mmol)溶解在干净的烧瓶中,然后在40℃的温度下加入5ml溴乙酸水溶液(1.7g,18mmol),同时 搅得顺利。 将反应混合物在60℃下搅拌5小时,然后通过冰浴冷却,用盐酸调节至pH5.5,通过膜过滤后,将粗产物用水重结晶,得到化合物2,为白色固体。 1.53克 产率85%,熔点255-257℃。 1 H NMR(400MHz,D 2 O):4.41(s,2H,N-CH 2),7.54(d,1H,J = 5.2Hz,5-FU-H),ESI MS(m / z):计算值188.11。 获取189.01([M + H] +)
参考文献:
- [1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 12, p. 3750 - 3756 [2] MedChemComm, 2016, vol. 7, # 10, p. 2016 - 2019 [3] Research on Chemical Intermediates, 2012, vol. 38, # 7, p. 1421 - 1429 [4] Patent: CN104672294, 2017, B. Location in patent: Paragraph 0033; 0034; 0035; 0037; 0038 [5] Pharmazie, 2014, vol. 69, # 4, p. 271 - 276 [6] Chemical Communications, 2011, vol. 47, # 5, p. 1482 - 1484 [7] Patent: CN107698521, 2018, A. Location in patent: Paragraph 0063; 0064; 0065 [8] Journal of Chemical Crystallography, 2008, vol. 38, # 11, p. 807 - 813 [9] Journal of Chemical Research, 2009, # 4, p. 261 - 264 [10] Letters in Organic Chemistry, 2013, vol. 10, # 8, p. 594 - 601 [11] European Journal of Medicinal Chemistry, 2017, vol. 125, p. 1235 - 1246 [12] MedChemComm, 2017, vol. 8, # 2, p. 385 - 389
合成路线 3(3. 合成:56059-30-4)
产率:81.8%
合成条件:at 18 - 25℃;
实验步骤:在100mL圆底烧瓶中加入VI-1(4·OOOg,18。50mmol),氢氧化钠(2·219g,55.49mmol)和水40mL,室温(18〜25°C)搅拌反应,TLC跟踪至 反应结束后,浓缩盐酸将pH调至约2,然后经过滤,干燥和重结晶过程,即得化合物V-1(2.846g),收率81.8%;白色固体; Ke点275-276℃。
参考文献:
- [1] Medicinal Chemistry Research, 2001, vol. 10, # 6, p. 390 - 403 [2] Patent: CN105294661, 2016, A. Location in patent: Paragraph 0037; 0038; 0039 [3] Heterocycles, 1989, vol. 28, # 2, p. 643 - 652