作为普纳替尼（普拉替尼）等酪氨酸激酶抑制剂（TKIs）的关键中间体，用于慢性髓细胞白血病（CML）和费城染色体阳性急性淋巴细胞白血病（Ph+ALL）等疾病的治疗药物研发与生产。
医药
路线1：催化加氢还原法
- 步骤：向4-甲基-1-(4-硝基-2-(三氟甲基)苄基)哌嗪（1.5g，5mmol）的MeOH（250mL）溶液中加入Raney镍（0.15g，10wt％）；在氢气氛（50psi）下搅拌24小时，TLC监测反应；反应混合物通过硅藻土过滤，滤液减压浓缩得产物（1.36g）。
- 条件：氢气、Raney镍，甲醇溶剂，反应24小时。
- 产率：100%。
- 参考文献：[1] Patent: US2014/31354, 2014, A1. Location in patent: Paragraph 0294; 0358; 0359 [2] Journal of Medicinal Chemistry, 2017, vol. 60, # 21, p. 8801 - 8815 [3] Journal of the American Chemical Society, 2013, vol. 135, # 5, p. 1669 - 1672 [4] Bioorganic Chemistry, 2016, vol. 68, p. 112 - 123 [5] Patent: WO2015/106292, 2015, A1. Location in patent: Paragraph 00605; 00608; 00609 [6] Journal of Medicinal Chemistry, 2010, vol. 53, # 12, p. 4701 - 4719 [7] Patent: EP1840122, 2007, A1. Location in patent: Page/Page column 12-13 [8] Patent: WO2007/75869, 2007, A2. Location in patent: Page/Page column 54 [9] Journal of Medicinal Chemistry, 2013, vol. 56, # 7, p. 3033 - 3047 [10] Patent: WO2013/162727, 2013, A1. Location in patent: Page/Page column 56 [11] Patent: WO2014/93579, 2014, A2. Location in patent: Page/Page column 107; 108 [12] European Journal of Medicinal Chemistry, 2017, vol. 130, p. 86 - 106 [13] Patent: CN106749278, 2017, A. Location in patent: Paragraph 0063; 0064; 0065; 0066 [14] Patent: US2017/305920, 2017, A1. Location in patent: Paragraph 0196 [15] Patent: WO2018/102751, 2018, A1. Location in patent: Paragraph 00218
路线2：酰胺还原法
- 步骤：将400mL THF加入2L反应釜，冷却至-5℃或更低，分批加入氢化铝锂50g（1.33mol，4.0eq），搅拌10min；继续冷却至-5℃或更低，滴加三氯化铝10g（0.0667mol，0.2eq）的THF溶液，保持温度低于5℃，搅拌30分钟；将产物酰胺96g（0.334mol，1.0eq）溶于500mL THF，在温度低于5℃时滴加，室温搅拌至TLC监测起始材料消失；冷却至0℃或更低，滴加水淬灭反应，过滤，滤液从甲苯中结晶得产物60.5g。
- 条件：氢化铝锂、三氯化铝，四氢呋喃溶剂，温度5-20℃。
- 产率：60%。
- 参考文献：[1] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 20, p. 7150 - 7163 [2] Patent: CN105461659, 2016, A. Location in patent: Paragraph 0032; 0033; 0034; 0065; 0066; 0067 [3] Patent: WO2015/186137, 2015, A1. Location in patent: Page/Page column 19 [4] Patent: WO2005/51366, 2005, A2. Location in patent: Page/Page column 62 [5] Patent: WO2005/51366, 2005, A2. Location in patent: Page/Page column 62
