High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

Eric Yu, Hari P. R. Mangunuru, Nakul S. Telang, Caleb J. Kong, Jenson Verghese, Stanley E. Gilliland III, Saeed Ahmad, Raymond N. Dominey and B. Frank Gupton
Beilstein J. Org. Chem. 2018, 14, 583–592. https://doi.org/10.3762/bjoc.14.45

Supporting Information

Supporting Information File 1: Additional experimental descriptions and NMR spectra.
Format: PDF Size: 920.8 KB Download

Cite the Following Article

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine
Eric Yu, Hari P. R. Mangunuru, Nakul S. Telang, Caleb J. Kong, Jenson Verghese, Stanley E. Gilliland III, Saeed Ahmad, Raymond N. Dominey and B. Frank Gupton
Beilstein J. Org. Chem. 2018, 14, 583–592. https://doi.org/10.3762/bjoc.14.45

How to Cite

Yu, E.; Mangunuru, H. P. R.; Telang, N. S.; Kong, C. J.; Verghese, J.; Gilliland III, S. E.; Ahmad, S.; Dominey, R. N.; Gupton, B. F. Beilstein J. Org. Chem. 2018, 14, 583–592. doi:10.3762/bjoc.14.45

Download Citation

Citation data can be downloaded as file using the "Download" button or used for copy/paste from the text window below.
Citation data in RIS format can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Zotero.

Presentation Graphic

Picture with graphical abstract, title and authors for social media postings and presentations.
Format: PNG Size: 208.4 KB Download

Citations to This Article

Up to 20 of the most recent references are displayed here.

Scholarly Works

  • Hyer, A.; Gregory, D.; Kay, K.; Le, Q.; Turnage, J.; Gupton, F.; Ferri, J. K. Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives. Advanced Synthesis & Catalysis 2024. doi:10.1002/adsc.202301137
  • Yalduz, S.; Eyilcim, Ö.; Kılıç, N.; Gülyüz, S.; Denizoğlu, O.; Zorlu, Y.; Ertürk, E. High-Yielding Process for the Synthesis of Hydroxychloroquine under Concentrated Conditions: Nucleophilic Amination of Chloropyridines Promoted by Dimethyl Sulfoxide or Catalyzed by 3,5-Bis(trifluoromethyl)phenol. Organic Process Research & Development 2023, 28, 137–151. doi:10.1021/acs.oprd.3c00220
  • Nemez, D. B.; Sidhu, B. K.; Carlin, K.; Friesen, A.; Herbert, D. E. Synthesis of novel 2- and 8-substituted 4-amino-7-chloroquinolines and their N-alkylated coupling products. Canadian Journal of Chemistry 2023, 101, 557–567. doi:10.1139/cjc-2023-0005
  • Wang, Z.; Sheaff, R. J.; Hussaini, S. R. Chloroquine-Based Mitochondrial ATP Inhibitors. Molecules (Basel, Switzerland) 2023, 28, 1161. doi:10.3390/molecules28031161
  • Singh, R.; Kumar Tyagi, Y.; Yadav, N. Hydroxychloroquine: Chemistry and Medicinal Applications. HETEROCYCLES 2023, 106, 423. doi:10.3987/rev-22-993
  • Chen, Y.; Monbaliu, J. M. doi:10.1002/9783527824595.ch7
  • Akwi, F. M.; Watts, P. doi:10.1002/9783527824595.ch6
  • Van Praet, S.; Preegel, G.; Rammal, F.; Sels, B. F. One-Pot Consecutive Reductive Amination Synthesis of Pharmaceuticals: From Biobased Glycolaldehyde to Hydroxychloroquine. ACS Sustainable Chemistry & Engineering 2022, 10, 6503–6508. doi:10.1021/acssuschemeng.2c00570
  • Chouhan, N. K.; Ananthabhat, S. K.; Vaidya, S.; Srihari, P. A scalable process for the synthesis of key intermediates novoldiamine & hydroxynovaldiamine and their utility in chloroquine, hydroxychloroquine and mepacrine synthesis. Synthetic Communications 2022, 52, 1004–1011. doi:10.1080/00397911.2022.2061358
  • Murugan, K.; Panneerselvam, C.; Subramaniam, J.; Paulpandi, M.; Rajaganesh, R.; Vasanthakumaran, M.; Madhavan, J.; Shafi, S. S.; Roni, M.; Portilla-Pulido, J. S.; Mendez, S. C.; Duque, J. E.; Wang, L.; Aziz, A. T.; Chandramohan, B.; Dinesh, D.; Piramanayagam, S.; Hwang, J.-S. Synthesis of new series of quinoline derivatives with insecticidal effects on larval vectors of malaria and dengue diseases. Scientific reports 2022, 12, 4765. doi:10.1038/s41598-022-08397-5
  • Burange, A. S.; Osman, S. M.; Luque, R. Understanding flow chemistry for the production of active pharmaceutical ingredients. iScience 2022, 25, 103892. doi:10.1016/j.isci.2022.103892
  • Malik, P.; Jain, S.; Jain, P.; Kumawat, J.; Dwivedi, J.; Kishore, D. A comprehensive update on the structure and synthesis of potential drug targets for combating the coronavirus pandemic caused by SARS-CoV-2. Archiv der Pharmazie 2022, 355, e2100382. doi:10.1002/ardp.202100382
  • Cue, B. W. Green chemistry approaches to drugs that treat epidemic and pandemic diseases. Contemporary Chemical Approaches for Green and Sustainable Drugs; Elsevier, 2022; pp 307–331. doi:10.1016/b978-0-12-822248-5.00003-6
  • Shagufta; Ahmad, I. An Update on Pharmacological Relevance and Chemical Synthesis of Natural Products and Derivatives with Anti SARS-CoV-2 Activity. ChemistrySelect 2021, 6, 11502–11527. doi:10.1002/slct.202103301
  • Rossi, F. V.; Gentili, D.; Marcantoni, E. Metal-Promoted Heterocyclization: A Heterosynthetic Approach to Face a Pandemic Crisis. Molecules (Basel, Switzerland) 2021, 26, 2620. doi:10.3390/molecules26092620
  • de Souza, A. A. N.; Paez, E. B. A.; de Assis, F. F.; Brocksom, T. J.; de Oliveira, K. T. Improved Synthesis of Bioactive Molecules Through Flow Chemistry. Topics in Medicinal Chemistry; Springer International Publishing, 2021; pp 317–371. doi:10.1007/7355_2021_117
  • Domokos, A.; Nagy, B.; Szilagyi, B.; Marosi, G.; Nagy, Z. K. Integrated Continuous Pharmaceutical Technologies—A Review. Organic Process Research & Development 2021, 25, 721–739. doi:10.1021/acs.oprd.0c00504
  • Adhikari, B.; Sahu, N. COVID-19 into Chemical Science Perspective: Chemical Preventive Measures and Drug Development. ChemistrySelect 2021, 6, 2010–2028. doi:10.1002/slct.202100127
  • Jiao, J.; Nie, W.; Yu, T.; Yang, F.; Zhang, Q.; Aihemaiti, F.; Yang, T.; Liu, X.; Wang, J.; Li, P. Multi-Step Continuous-Flow Organic Synthesis: Opportunities and Challenges. Chemistry (Weinheim an der Bergstrasse, Germany) 2021, 27, 4817–4838. doi:10.1002/chem.202004477
  • Li, D.; Hu, J.; Li, D.; Yang, W.; Yin, S.-F.; Qiu, R. Reviews on Biological Activity, Clinical Trial and Synthesis Progress of Small Molecules for the Treatment of COVID-19. Topics in current chemistry (Cham) 2021, 379, 4. doi:10.1007/s41061-020-00318-2

Patents

  • ROSSI ROBERTO; RAZZETTI GABRIELE; MANTEGAZZA SIMONE. PROCEDIMENTO PER LA PREPARAZIONE DI UN AGENTE PER IL TRATTAMENTO DELLA MALARIA. IT 202000020872 A1, March 2, 2022.
  • GUPTON FRANK B; AHMAD SAEED; GUNURU HARI P R; TELANG NAKUL S. HIGH-YIELDING CONTINUOUS FLOW SYNTHESIS OF ANTIMALARIAL DRUG HYDROXYCHLOROQUINE. US 20200407321 A1, Dec 31, 2020.
Other Beilstein-Institut Open Science Activities