Home

Citation: Fan Lingling, Luo Zhongfu, Luo Bilan, Tang Lei, Li Yong. Optimization of Synthetic Process for the CRBN Regulator Avadomide[J]. Chemistry, ;2019, 82(9): 837-841. shu

Optimization of Synthetic Process for the CRBN Regulator Avadomide

College of Pharmacy, Guizhou Medical University, Guiyang 550025

Corresponding author: Li Yong, liyong19851016@126.com
Received Date: 26 June 2019
Accepted Date: 18 July 2019

Figures(2)

Avadomide is a potential drug for the treatment of advanced solid tumors, which is in phase Ⅱ clinical trials. In this work, the synthetic process of Avadomide was optimized and improved. Using 3-nitrophthalimide as the starting material, Avadomide was obtained by ring-cleavage, Hoffman degradation, cyclization, ester aminolysis reaction and Pd(OH)₂/C hydrogenation reduction. The overall yield was 46.9%, and the target compound was identified by ¹H NMR, ¹³C NMR and HRMS, whose purity was 99.5% through HPLC test. In comparison with literature methods, this synthetic route has the advantages of mild reaction conditions, simple post-treatment, high yield and easy work-up, so it is suitable for industrial production of Avadomide.
- CRBN regulator,
- Avadomide,
- Process optimization
1. [1]
  D W Rasco, A K Gandhi, A James et al. Blood, 2013, 122(21):2905~2906.
2. [2]
  P R Hagner, H W Man, C Fontanillo et al. Blood, 2015, 126(6):779~789.
3. [3]
  T M W Burnell, H Patrick, C G Havens et al. WO: 2015085172, 2015.
4. [4]
5. [5]
  D W Rasco, K P Papadopoulos, M Pourdehnad et al. Clin. Cancer Res., 2019, 25(1):1~25.
6. [6]
  G W Muller, P H Schafer, H W Man. WO: 2008039489, 2008.
7. [7]
  J Kronke, E C Fink, P W Hollenbach et al. Nature, 2015, 523(7559):183~188.
8. [8]
  L F Huang, D Z Zou. WO: 2018165142, 2018.
9. [9]
  A J Phillips, C G Nasveschuk, J A Henderson et al. WO: 2017197056, 2017.
10. [10]
  B Dennis, W Georg, A J Phillips et al. WO: 2017024319, 2017.
11. [11]
  U Nagai. Chem. Pharm. Bull., 1975, 23(8):1841~1844.
12. [12]
  G W Muller, P H Schafer, H W Man et al. US: 2012230983, 2012.
1. [1]
  Haifeng Ma , Xiaocong Tian , Fengbin Wang , Zhonghua Xi , QingWang . Design of College Chemistry Experiment Based on Product Quality Control: Taking “Optimization of Ferrous Fumarate Synthesis Process” as an Example. University Chemistry, 2025, 40(7): 321-327. doi: 10.12461/PKU.DXHX202409056
2. [2]
  Zhao Lu , Hu Lv , Qinzhuang Liu , Zhongliao Wang . Modulating NH₂ Lewis Basicity in CTF-NH₂ through Donor-Acceptor Groups for Optimizing Photocatalytic Water Splitting. Acta Physico-Chimica Sinica, 2024, 40(12): 2405005-0. doi: 10.3866/PKU.WHXB202405005
3. [3]
  Jiandong Liu , Xin Li , Daxiong Wu , Huaping Wang , Junda Huang , Jianmin Ma . Anion-Acceptor Electrolyte Additive Strategy for Optimizing Electrolyte Solvation Characteristics and Electrode Electrolyte Interphases for Li||NCM811 Battery. Acta Physico-Chimica Sinica, 2024, 40(6): 2306039-0. doi: 10.3866/PKU.WHXB202306039
4. [4]
  Shahua Huang , Xiaoming Guo , Lin Lin , Guangping Chang , Sheng Han , Zuxin Zhou . Application of “Integration of Industry and Education” in Engineering Chemistry: Improvement of the Pesticide Fipronil Production. University Chemistry, 2024, 39(3): 199-204. doi: 10.3866/PKU.DXHX202309064
5. [5]
  Bingliang Li , Yuying Han , Dianyang Li , Dandan Liu , Wenbin Shang . One-Step Synthesis of Benorilate Guided by Green Chemistry Principles and in vivo Dynamic Evaluation. University Chemistry, 2024, 39(6): 342-349. doi: 10.3866/PKU.DXHX202311070
6. [6]
  Jianfu Zhang , Wei Bai , Juan Hou , Chenyang Zou . Reform and Practice of “Project-Patent- Scholarly Paper” Integrated Teaching Mode: Taking “Polymer Processing” Course as an Example. University Chemistry, 2025, 40(4): 138-146. doi: 10.12461/PKU.DXHX202408138
7. [7]
  Siyu Zhang , Kunhong Gu , Bing'an Lu , Junwei Han , Jiang Zhou . Hydrometallurgical Processes on Recycling of Spent Lithium-lon Battery Cathode: Advances and Applications in Sustainable Technologies. Acta Physico-Chimica Sinica, 2024, 40(10): 2309028-0. doi: 10.3866/PKU.WHXB202309028
8. [8]
  Xiaofang Li , Zhigang Wang . 调节金助催化剂的d_z²占据轨道增强光催化合成H₂O₂. Acta Physico-Chimica Sinica, 2025, 41(7): 100080-0. doi: 10.1016/j.actphy.2025.100080
9. [9]
  Qian Peng , Pengfei Yao , Zicong Wang , Xiufang Xu , Hongwei Sun . Promote the Training of Top Talents by Optimizing the Theoretical Computational Chemistry Curriculum System. University Chemistry, 2025, 40(5): 261-267. doi: 10.12461/PKU.DXHX202408012
10. [10]
  Feixue Gao , Lu Zhao , Xiangjian Shen , Junlin Yang , Yongjun Chen . Optimizing the Funding Allocation in Physical Chemistry, Improving the Grant Effectiveness of Science Foundation. Acta Physico-Chimica Sinica, 2024, 40(3): 2309009-0. doi: 10.3866/PKU.WHXB202309009
11. [11]
  Lisen Sun , Yongmei Hao , Zhen Huang , Yongmei Liu . Experimental Teaching Design for Viscosity Measurement Serves the Optimization of Operating Conditions for Kitchen Waste Treatment Equipment. University Chemistry, 2024, 39(2): 52-56. doi: 10.3866/PKU.DXHX202307063
12. [12]
  Jiaojiao Yu , Bo Sun , Na Li , Cong Wen , Wei Li . Improvement of Classical Organic Experiment Based on the “Reverse-Step Optimization Method”: Taking Synthesis of Ethyl Acetate as an Example. University Chemistry, 2025, 40(3): 333-341. doi: 10.12461/PKU.DXHX202405177
13. [13]
  Pengyu Dong , Yue Jiang , Zhengchi Yang , Licheng Liu , Gu Li , Xinyang Wen , Zhen Wang , Xinbo Shi , Guofu Zhou , Jun-Ming Liu , Jinwei Gao . NbSe₂ Nanosheets Improved the Buried Interface for Perovskite Solar Cells. Acta Physico-Chimica Sinica, 2025, 41(3): 2407025-0. doi: 10.3866/PKU.WHXB202407025
14. [14]
  Fangfang Chen , Haiming Fan , Yan Li , Yuan He . 化学生物学专业多元化人才培养导向的课程体系优化探索. University Chemistry, 2025, 40(8): 92-99. doi: 10.12461/PKU.DXHX202409108
15. [15]
  Hui Li , Wei Cheng , Meng Yu , Yi Li . Improving Postgraduate Cultivation in Chemistry Discipline: A Case Study of the Chemistry Program in Jilin University. University Chemistry, 2024, 39(6): 17-22. doi: 10.3866/PKU.DXHX202403047
16. [16]
  Fanpeng Meng , Fei Zhao , Jingkai Lin , Jinsheng Zhao , Huayang Zhang , Shaobin Wang . Optimizing interfacial electric fields in carbon nitride nanosheet/spherical conjugated polymer S-scheme heterojunction for hydrogen evolution. Acta Physico-Chimica Sinica, 2025, 41(8): 100095-0. doi: 10.1016/j.actphy.2025.100095
17. [17]
  Ying Liang , Yuheng Deng , Shilv Yu , Jiahao Cheng , Jiawei Song , Jun Yao , Yichen Yang , Wanlei Zhang , Wenjing Zhou , Xin Zhang , Wenjian Shen , Guijie Liang , Bin Li , Yong Peng , Run Hu , Wangnan Li . Machine learning-guided antireflection coatings architectures and interface modification for synergistically optimizing efficient and stable perovskite solar cells. Acta Physico-Chimica Sinica, 2025, 41(9): 100098-0. doi: 10.1016/j.actphy.2025.100098
18. [18]
  Qianwen Han , Tenglong Zhu , Qiuqiu Lü , Mahong Yu , Qin Zhong . Performance and Electrochemical Asymmetry Optimization of Hydrogen Electrode Supported Reversible Solid Oxide Cell. Acta Physico-Chimica Sinica, 2025, 41(1): 100005-0. doi: 10.3866/PKU.WHXB202309037
19. [19]
  Shi-Yu Lu , Wenzhao Dou , Jun Zhang , Ling Wang , Chunjie Wu , Huan Yi , Rong Wang , Meng Jin . Amorphous-Crystalline Interfaces Coupling of CrS/CoS₂ Few-Layer Heterojunction with Optimized Crystallinity Boosted for Water-Splitting and Methanol-Assisted Energy-Saving Hydrogen Production. Acta Physico-Chimica Sinica, 2024, 40(8): 2308024-0. doi: 10.3866/PKU.WHXB202308024
20. [20]
  Xueqi Yang , Juntao Zhao , Jiawei Ye , Desen Zhou , Tingmin Di , Jun Zhang . 调节NNU-55(Fe)的d带中心以增强CO₂吸附和光催化活性. Acta Physico-Chimica Sinica, 2025, 41(7): 100074-0. doi: 10.1016/j.actphy.2025.100074

Get Citation

PDF

XML

Metrics

PDF Downloads(10)
Abstract views(803)
HTML views(160)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Address：Zhongguancun North First Street 2,100190 Beijing, PR China Tel: +86-010-82449177-888

DownLoad: Full-Size Img PowerPoint

Return