作为医药中间体用于制备将内源蛋白质募集至E3泛素连接酶以进行降解的化合物;在PROTAC化合物合成中充当试剂,介导致癌的c-ABL和BCR-ABL降解;作为小分子配体,结合VHL蛋白用于靶向蛋白质降解和PROTAC技术;用于实验室研发和化工医药合成过程
医药中间体;有机合成中间体
合成路线 1(1. 合成:1448189-80-7)
- 步骤:向搅拌的N-[(2S)-1-[(2S,4R)-4-羟基-2-({4-(4-甲基-1,3-噻唑-5-基)苯基]甲基氨基甲酰基)吡咯烷-1-基]-3,3-二甲基-1-氧代丁烷-2-基]氨基甲酸酯(12 g, 22.61 mmol)在二氧六环(20 mL)溶液中加入氯化氢的二恶烷溶液(4N, 80 mL),室温下搅拌2小时,LC-MS表明形成所需产物。
- 条件:With hydrogenchloride In 1,4-dioxane at 20℃; for 2 h
- 产率:48%
- 产物:通过过滤收集沉淀的固体,得到ULM-1(黄色固体)
- 表征:1HNMR(400MHz,CD3OD):δ9.84-9.82(s,1H),7.58-7.54(m,4H),4.71-4.41(m,4H),4.13-4.08(m,1H),3.86-3.71(m,2H),3.36(s,1H),2.60-2.58(s,3H),2.35-2.07(m,2H),1.19-1.12(m,9H);LC-MS(ES+):m/z 431.11 [MH+],t R=0.73min(运行2.0分钟)
- 参考文献:[1] Patent: WO2016/118666, 2016, A1. Location in patent: Paragraph 0398; 0399; 0411; 0412 [2] Patent: US2017/8904, 2017, A1. Location in patent: Paragraph 0376; 0382 [3] Patent: US2017/281784, 2017, A1. Location in patent: Paragraph 0191; 0197 [4] Patent: US2018/125821, 2018, A1 [5] Patent: WO2014/108452, 2014, A1. Location in patent: Page/Page column 50 [6] Patent: WO2015/867, 2015, A1. Location in patent: Page/Page column 46-47 [7] Journal of Medicinal Chemistry, 2018, vol. 61, # 2, p. 583 - 598 [8] Patent: US2016/45607, 2016, A1. Location in patent: Paragraph 0279; 0280