19171-19-8 泊马度胺

运输方式：冰袋运输。危险性质：非危险化学品。WGK Germany:3，RTECS号:NR3397905，海关编码:29251900，存储类别:6.1C（可燃，急性毒性类别3，毒性化合物或引起慢性影响的化合物），危险性类别:生殖毒性类别1B，毒害物质数据:19171-19-8(Hazardous Substances Data)

化学合成；生命科学；医药，是一种有抗肿瘤活性的免疫调节剂。泊马度胺是第三代免疫调节剂，可增强T细胞和自然杀伤细胞介导的免疫反应、抑制单核细胞促炎性细胞因子的生成、诱导肿瘤细胞凋亡，用于各类恶性肿瘤、免疫性疾病的治疗，尤其在多发性骨髓瘤前期临床研究中效果显著。

医药

合成路线 1（1. 合成：19171-19-8）

产率：93.3% 合成条件：With palladium 10% on activated carbon; hydrogen In water; N,N-dimethyl-formamide at 35℃; for 3 h; 实验步骤：向反应烧瓶中加入33-硝基-N-（2,6-二氧代-3-哌啶基）邻苯二甲酰亚胺（II）（100.0g，0.33mol），10％钯碳12.0g，DMF 1000ml，70ml水，真空，引入氢气（更换三次），反应常压在35°C下保持3h，TLC监测反应完成，滤出钯碳，将DMF溶液缓慢加入5倍量的水中，搅拌约30分钟后，过滤固体，用适量水洗涤滤饼（2L * 3次，30分钟/次），滤饼用200ml乙醇洗涤，固体转移至3L烧瓶中加入2L乙酸乙酯，在73℃搅拌0.5小时，热过滤，将固体在45℃下干燥至恒重，得到黄色固体粉末84.1g，收率93.3％。HPLC纯度百分比99.9。 参考文献：[1] Patent: CN105348257, 2016, A. Location in patent: Paragraph 0051; 0052; 0053 [2] Patent: CN106565668, 2017, A. Location in patent: Paragraph 0053; 0054; 0055; 0056-0061 [3] Patent: CN104557858, 2018, B. Location in patent: Paragraph 0032; 0033; 0036; 0038; 0040; 0042; 0044; 0046 [4] Patent: CN103804350, 2016, B. Location in patent: Paragraph 0029; 0031 [5] Patent: US2017/260157, 2017, A1. Location in patent: Paragraph 0057; 0058; 0059; 0060; 0061; 0062; 0063 [6] Synthetic Communications, 2016, vol. 46, # 16, p. 1343 - 1348 [7] Patent: WO2018/148440, 2018, A1. Location in patent: Page/Page column 297; 300; 301 [8] Patent: WO2018/148443, 2018, A1. Location in patent: Page/Page column 281-282 [9] Bioorganic Chemistry, 2018, vol. 81, p. 536 - 544 [10] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 11, p. 1625 - 1630 [11] Chemical and Pharmaceutical Bulletin, 2006, vol. 54, # 6, p. 855 - 860 [12] Patent: US6335/349, 2002, B1. Location in patent: Example 1 [13] Patent: US6335349, 2002, B1. Location in patent: Example 1 [14] Patent: US2013/143922, 2013, A1. Location in patent: Paragraph 0091 [15] Patent: WO2014/170909, 2014, A2. Location in patent: Page/Page column 5 [16] Patent: WO2015/75694, 2015, A1. Location in patent: Page/Page column 2; 4; 9 [17] Patent: CN104402863, 2016, B. Location in patent: Paragraph 0035 [18] Patent: CN107188884, 2017, A. Location in patent: Paragraph 0019; 0033; 0034; 0036 [19] Patent: CN107365295, 2017, A. Location in patent: Paragraph 0014; 0015 [20] Patent: WO2017/221261, 2017, A1. Location in patent: Page/Page column 5; 6 [21] Patent: WO2018/154516, 2018, A1. Location in patent: Page/Page column 8 [22] ACS Chemical Biology, 2018, vol. 13, # 9, p. 2771 - 2782