化学合成。
化学合成
合成路线 1（1. 合成：723281-72-9）
产率：100%
合成条件：for 0.75 h; Reflux
实验步骤：上述反应方案说明了本发明化合物2-13的合成。 原料2-1的甲基化得到化合物2-2，随后将其还原成胺2-3。 在单独的反应中，将化合物2-4转化为盐，例如HCl盐，然后使其与例如2-硝基乙烯基 - 羟胺反应，得到化合物2-6。 进一步环化得到化合物2-7。 用诸如POd3的试剂进行卤化，得到化合物2-8，其可以与中间体2-3偶合，得到2-9。 随后将2-9的硝基部分还原成胺，并且与4-硝基苯基氯甲酸酯的进一步反应产生杂环2-11。 然后通过与苯并恶唑基硼酸酯2-12偶合，例如在Suzuki偶联中制备所需的化合物2-13。
参考文献：
- [1] Patent: US2015/320727, 2015, A1. Location in patent: Paragraph 0555; 0556 [2] Patent: WO2015/145369, 2015, A1. Location in patent: Page/Page column 38 [3] Patent: WO2009/155527, 2009, A2. Location in patent: Page/Page column 142 [4] MedChemComm, 2016, vol. 7, # 2, p. 297 - 310 [5] Patent: CN108456165, 2018, A. Location in patent: Paragraph 0047; 0081-0082 [6] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 3, p. 799 - 807 [7] Patent: EP3072893, 2016, A1. Location in patent: Paragraph 0071; 0074 [8] Patent: CN104411706, 2016, B. Location in patent: Paragraph 0197-0198 [9] Archiv der Pharmazie, 2018, vol. 351, # 6, [10] Patent: WO2011/1212, 2011, A1. Location in patent: Page/Page column 38 [11] Patent: US2012/108627, 2012, A1. Location in patent: Page/Page column 15-16 [12] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 3, p. 1027 - 1030 [13] Patent: WO2005/54237, 2005, A1. Location in patent: Page/Page column 53-54 [14] Patent: WO2005/54238, 2005, A1. Location in patent: Page/Page column 63 [15] Patent: WO2008/64093, 2008, A2. Location in patent: Page/Page column 17 [16] Patent: WO2007/75468, 2007, A1. Location in patent: Page/Page column 71 [17] Patent: WO2010/139731, 2010, A1. Location in patent: Page/Page column 94 [18] Patent: WO2012/7926, 2012, A1. Location in patent: Page/Page column 47 [19] Patent: WO2012/77031, 2012, A1. Location in patent: Page/Page column 42-43 [20] Patent: WO2012/116237, 2012, A2. Location in patent: Page/Page column 119 [21] Patent: WO2013/23119, 2013, A1. Location in patent: Page/Page column 27 [22] Patent: WO2014/141118, 2014, A1. Location in patent: Page/Page column 45 [23] Patent: WO2014/151147, 2014, A1. Location in patent: Paragraph 00641 [24] Patent: US2015/30588, 2015, A1. Location in patent: Page/Page column 74 [25] Patent: US9295673, 2016, B2. Location in patent: Page/Page column 360 [26] Patent: US9358229, 2016, B2. Location in patent: Page/Page column 18 [27] Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6337 - 6352 [28] Molecules, 2018, vol. 23, # 7, [29] Patent: CN108503634, 2018, A. Location in patent: Paragraph 0274; 0275; 0280; 0281 [30] Patent: WO2006/122806, 2006, A2. Location in patent: Page/Page column 48 [31] Patent: WO2010/139747, 2010, A1. Location in patent: Page/Page column 78
合成路线 2（2. 合成：723281-72-9）
产率：53%
合成条件：at 120℃; for 1 h;
实验步骤：将26.8g（99mmol）中间体2置于500ml单颈烧瓶中，加入200ml磷酰氯，并在120℃下回流1小时。 通过TLC监测反应。 反应完成后，将反应混合物倒入大量冰水中并搅拌，导致形成沉淀。 过滤反应混合物，滤饼用冰水洗涤，然后溶解在二氯甲烷中。 将有机相用盐水洗涤三次，用无水硫酸镁干燥，旋转蒸发至干，得到16.1g中间体3.产率：53％。
参考文献：
- [1] Patent: EP3072893, 2016, A1. Location in patent: Paragraph 0074
