837-52-5 7-氯-4-(1-哌嗪基)喹啉

运输方式：冰袋运输。危险描述：非危险化学品，WGK Germany 3，具有腐蚀性和刺激性，海关编码2933499090，存储类别11 - 可燃固体。

喹哌磷酸盐的中间体。

医药

合成路线 1（1. 合成：837-52-5）

• 步骤: 将4,7-二氯喹啉（2.00g，10.1mmol）与哌嗪（4.35g，50.5mmol，5.0当量）和纯三乙胺（2.81mL，20.2mmol，2.0当量）合并。将反应烧瓶在氮气下密封并加热至130℃，随后固体材料逐渐熔化，得到澄清的橙黄色溶液。一段时间后，观察到黄色沉淀。通过TLC测定反应在约4小时内完成（使用5％v / v甲醇的二氯甲烷溶液作为溶剂体系）。此时，将反应冷却至室温，然后用二氯甲烷（25mL）和水（25mL）稀释。分离各层，有机层用水（3×25mL）洗涤。然后将合并的含水洗涤液用二氯甲烷（50mL）反萃取。将合并的有机层用盐水（50mL）洗涤，用硫酸镁干燥，过滤，并减压浓缩，得到黄色固体（2.60g）。通过硅胶柱色谱（二氯甲烷/甲醇：100/0至98/2）纯化粗物质，得到2.44g（9.85mmol，98％产率）标题化合物，为黄色固体。
• 条件: at 130℃; for 4 h; Inert atmosphere
• 收率: 98%
• 参考文献: [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5502 - 5505 [2] Indian Journal of Heterocyclic Chemistry, 2010, vol. 19, # 3, p. 215 - 220 [3] Journal of Medicinal Chemistry, 1998, vol. 41, # 22, p. 4360 - 4364 [4] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 10, p. 2882 - 2886 [5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 17, p. 4733 - 4736 [6] Molecules, 2009, vol. 14, # 4, p. 1483 - 1494 [7] Arzneimittel-Forschung/Drug Research, 2010, vol. 60, # 10, p. 627 - 635 [8] Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 916 - 919 [9] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 17, p. 6451 - 6462 [10] Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 1, p. 97 - 102 [11] Journal of Heterocyclic Chemistry, 2015, vol. 52, # 4, p. 1108 - 1113 [12] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3637 - 3649 [13] Archiv der Pharmazie, 2017, vol. 350, # 3-4, [14] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 11, p. 3080 - 3089 [15] European Journal of Medicinal Chemistry, 2014, vol. 75, p. 67 - 76 [16] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 1, p. 269 - 277 [17] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 4, p. 1563 - 1572 [18] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 9, p. 3249 - 3261 [19] Medicinal Chemistry Research, 2014, vol. 23, # 3, p. 1214 - 1224 [20] European Journal of Medicinal Chemistry, 2016, vol. 122, p. 216 - 231 [21] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1995, vol. 34, # 2, p. 164 - 166 [22] Molecules, 2008, vol. 13, # 10, p. 2426 - 2441 [23] Medicinal Chemistry Research, 2016, vol. 25, # 9, p. 1993 - 2004 [24] Patent: US2006/270852, 2006, A1. Location in patent: Page/Page column 2-3 [25] Patent: EP1308439, 2003, A1 [26] Patent: WO2004/2960, 2004, A1. Location in patent: Page 52 [27] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 23, p. 7059 - 7063 [28] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 6, p. 1683 - 1686 [29] Patent: WO2011/95885, 2011, A1. Location in patent: Page/Page column 9-10 [30] South African Journal of Chemistry, 2011, vol. 64, p. 163 - 172 [31] Patent: WO2012/168213, 2012, A2. Location in patent: Page/Page column 6-7 [32] European Journal of Medicinal Chemistry, 2013, vol. 66, p. 69 - 81 [33] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 10, p. 1005 - 1010 [34] European Journal of Medicinal Chemistry, 2014, vol. 74, p. 657 - 663 [35] Chemical Biology and Drug Design, 2014, vol. 83, # 5, p. 622 - 629 [36] RSC Advances, 2014, vol. 4, # 40, p. 20729 - 20736 [37] Patent: WO2014/134705, 2014, A1. Location in patent: Paragraph 00236-00237 [38] Journal of Medicinal Chemistry, 2014, vol. 57, # 16, p. 7042 - 7060 [39] European Journal of Medicinal Chemistry, 2014, vol. 84, # C, p. 566 - 573 [40] RSC Advances, 2015, vol. 5, # 60, p. 48368 - 48381 [41] European Journal of Medicinal Chemistry, 2017, vol. 125, p. 269 - 277 [42] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 3, p. 460 - 465 [43] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 3, p. 941 - 948 [44] Chemical Biology and Drug Design, 2017, vol. 90, # 4, p. 590 - 595 [45] Drug Research, 2018, vol. 68, # 1, p. 17 - 22 [46] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 8, p. 1309 - 1312