571188-59-5 4-(6-氨基吡啶-3-基)哌嗪-1-羧酸叔丁酯

危险性质：非危险化学品

化学合成，医药哌泊塞克雷布中间体。

4-(6-氨基吡啶-3-基)哌嗪-1-羧酸叔丁酯是医药中间体，主要用于合成帕布昔利布原料药。

合成路线 1（1. 合成：571188-59-5）

产率：99.1% 合成条件：With palladium 10% on activated carbon; hydrogen In methanol at 25℃; for 4 h; Autoclave 实验步骤：步骤b）：4-（6-氨基 - 吡啶-3-基） - 哌嗪-1-羧酸叔丁酯的合成式4）步骤b）：向10L高压釜中加入328.2g硝基-1- Boc-4-（6-硝基-3-吡啶基）哌嗪（式3）（1.064mol，1.00当量）和3.5L MeOH。用N 2吹扫该体系。然后一次性加入22.7g 10％Pd / C（50％湿润，21.3mmol，0.02当量）。在搅拌（300转/分）的同时，再次用N 2（2×2巴）吹扫反应器，然后加压至3巴氢气。将反应混合物的温度设定为25℃。 4小时后，混合物的IPC显示原料完全消耗。小心地从高压釜中抽空氢气并过滤混合物。用200ml MeOH冲洗固体，减压浓缩滤液。将残余物溶于250ml甲苯中，再次在减压下浓缩并在50℃/ 15mbar下干燥8小时，得到293.5g 4-（6-氨基 - 吡啶-3-基） - 哌嗪-1-羧酸叔丁酯（式4），为浅紫色固体（99.1％收率）.HLC（方法2）：6.65min（99.6％）（246nm）。 参考文献：

• [1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 6, p. 3125 - 3140 [2] Patent: WO2016/30439, 2016, A1. Location in patent: Page/Page column 30 [3] Patent: WO2011/140488, 2011, A1. Location in patent: Page/Page column 112; 270 [4] Patent: US2013/116262, 2013, A1. Location in patent: Paragraph 0315 [5] Patent: EP2773638, 2015, B1. Location in patent: Paragraph 0170; 0171; 1405 [6] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 6, p. 608 - 613 [7] Patent: CN108822026, 2018, A. Location in patent: Paragraph 0045-0046; 0049; 0053-0054; 0056; 0060-0061; 0062 [8] Patent: WO2014/128588, 2014, A1. Location in patent: Page/Page column 33 [9] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 2, p. 348 - 364 [10] European Journal of Medicinal Chemistry, 2018, vol. 144, p. 1 - 28 [11] Patent: EP3269715, 2018, A1. Location in patent: Paragraph 0123; 0124 [12] Patent: CN108558745, 2018, A. Location in patent: Paragraph 0030; 0031 [13] Patent: WO2010/20675, 2010, A1. Location in patent: Page/Page column 50; 51 [14] Patent: WO2008/7123, 2008, A2. Location in patent: Page/Page column 115 [15] Patent: US2012/115878, 2012, A1. Location in patent: Page/Page column 9-10 [16] Patent: CN106608879, 2017, A. Location in patent: Paragraph 0154-0155; 0159-0160 [17] Patent: CN106905245, 2017, A. Location in patent: Paragraph 0304; 0309; 0310; 0311; 0312 [18] Medicinal Chemistry Research, 2018, vol. 27, # 6, p. 1666 - 1678 [19] Patent: CN107674022, 2018, A. Location in patent: Paragraph 0034; 0035; 0036; 0037; 0038; 0039-0054 [20] Patent: WO2016/55786, 2016, A1. Location in patent: Paragraph 00260 [21] Patent: EP2429566, 2016, B1. Location in patent: Page/Page column 21 [22] Patent: US9808461, 2017, B2. Location in patent: Page/Page column 22 [23] Patent: EP3284746, 2018, A1. Location in patent: Paragraph 0096 [24] Patent: WO2008/32157, 2008, A2. Location in patent: Page/Page column 25 [25] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2388 - 2406 [26] Journal of Medicinal Chemistry, 2017, vol. 60, # 5, p. 1892 - 1915 [27] Patent: EP3305785, 2018, A1. Location in patent: Paragraph 0174; 0175 [28] Patent: WO2014/195274, 2014, A1. Location in patent: Page/Page column 49 [29] Patent: WO2006/95159, 2006, A1. Location in patent: Page/Page column 78 [30] Patent: WO2006/8545, 2006, A2. Location in patent: Page/Page column 153 [31] Patent: WO2010/101849, 2010, A1. Location in patent: Page/Page column 61 [32] Journal of Medicinal Chemistry, 2010, vol. 53, # 22, p. 7938 - 7957 [33] Patent: WO2012/97682, 2012, A1. Location in patent: Page/Page column 158 [34] European Journal of Medicinal Chemistry, 2014, vol. 81, p. 341 - 349 [35] Patent: WO2015/131080, 2015, A1. Location in patent: Paragraph 00669; 00671 [36] Patent: CN105622638, 2016, A. Location in patent: Paragraph 0200 [37] Patent: CN106749259, 2017, A. Location in patent: Paragraph 0013; 0048; 0111; 0123; 0135 [38] Patent: CN105153149, 2017, B. Location in patent: Page/Page column 2; 7; 8; 9 [39] Journal of Medicinal Chemistry, 2018, vol. 61, # 6, p. 2227 - 2245 [40] British Journal of Pharmacology, 2018, vol. 175, # 12, p. 2399 - 2413 [41] Journal of Medicinal Chemistry, 2018, [42] Patent: EP3385262, 2018, A1. Location in patent: Paragraph 0076; 0077; 0078