ABT-492 synthesis

Delafloxacin, also known as ABT-492, RX-3341 and WQ-3034, is a non-zwitterionic fluoroquinolone antibiotic under development for for the treatment of respiratory and skin infections. Delafloxacin demonstrates excellent antibacterial potency and exhibits a low probability for the selection of resistant mutants in MRSA. Although mutants can be selected at low frequencies in vitro from quinolone-resistant isolates, delafloxacin MICs and MPCs remain low and a fitness cost can be observed. Consequently delafloxacin warrants further investigation for the potential treatment of drug-resistant MRSA infections. Synthetic Description Reference: Roger Hanselmann, Graham Johnson, Maxwell M. Reeve, and Shu-Ting Huang. Identification and Suppression of a Dimer Impurity in the Development of Delafloxacin. Organic Process Research & Development 2009 13 (1), 54-59. DOI: 10.1021/op800238q Synthetic Description Reference: Barnes, David & Christesen, Alan & M. Engstrom, Kenneth & Haight, Anthony & C. Hsu, Margaret & C. Lee, Elaine & J. Peterson, Matthew & J. Plata, Daniel & S. Raje, Prasad & Stoner, Eric & Tedrow, Jason & Wagaw, Seble. (2006). Chlorination at the 8Position of a Functionalized Quinolone and the Synthesis of Quinolone Antibiotic ABT-492. Organic Process Research & Development - ORG PROCESS RES DEV. 10. 803-807. 10.1021/op0600557. Synthetic Description Reference: Hanselmann, Roger; Reeve, Maxwell M.; Johnson, Graham. Process for making quinolone compounds useful as anti-infective agents. WO 2010036329. (Assignee Rib-X Pharmaceuticals, Inc., USA) Synthetic Description Reference: Zhang, Weifeng; Xing, Wenli; Luo, Lin. Preparation method of antibacterial drug delafloxacin and its intermediate. CN 108084161. (Assignee Beijing Voban Pharmaceutical Technology Co., Ltd., Peop. Rep. China) Synthetic Description Reference: Kong, Rui; Yuan, Zhedong; Liu, Xiangkui; Chen, Shan. Delafloxacin intermediate and preparation method thereof. CN 103936717. (Assignee Shanghai Institute of Pharmaceutical Industry, Peop. Rep. China; China State Institute of Pharmaceutical Industry) Synthetic Description Reference: Xiao, Tao; Wang, Xiaoming; Feng, Yi; Tian, Xin; Li, Song. Simple synthesis method of delafloxacin. CN 104876911. (Assignee Nanjing Tech University, Peop. Rep. China) Synthetic Description Reference: Pan, Yuan; Zuo, Xiaoyong; Zhang. Preparation method of highly purified delafloxacin meglumine. CN 106256824. (Assignee Chongqing Pharmaceutical Research Institute Co., Ltd., Peop. Rep. China) Synthetic Description Reference: Zhang, Guimin; Wang, Xiujuan; Zhao, Xuliang; Wu, Suzhen. Method for preparation of delafloxacin. CN 107778293. (Assignee Lunan Pharmaceutical Group Corp., Peop. Rep. China)

• ROUTE 1



Reference: Roger Hanselmann, Graham Johnson, Maxwell M. Reeve, and Shu-Ting Huang. Identification and Suppression of a Dimer Impurity in the Development of Delafloxacin. Organic Process Research & Development 2009 13 (1), 54-59. DOI: 10.1021/op800238q

• ROUTE 2



Reference: Barnes, David & Christesen, Alan & M. Engstrom, Kenneth & Haight, Anthony & C. Hsu, Margaret & C. Lee, Elaine & J. Peterson, Matthew & J. Plata, Daniel & S. Raje, Prasad & Stoner, Eric & Tedrow, Jason & Wagaw, Seble. (2006). Chlorination at the 8Position of a Functionalized Quinolone and the Synthesis of Quinolone Antibiotic ABT-492. Organic Process Research & Development - ORG PROCESS RES DEV. 10. 803-807. 10.1021/op0600557.

• ROUTE 3



Reference: Hanselmann, Roger; Reeve, Maxwell M.; Johnson, Graham. Process for making quinolone compounds useful as anti-infective agents. WO 2010036329. (Assignee Rib-X Pharmaceuticals, Inc., USA)

• ROUTE 4



Reference: Zhang, Weifeng; Xing, Wenli; Luo, Lin. Preparation method of antibacterial drug delafloxacin and its intermediate. CN 108084161. (Assignee Beijing Voban Pharmaceutical Technology Co., Ltd., Peop. Rep. China)

• ROUTE 5



Reference: Kong, Rui; Yuan, Zhedong; Liu, Xiangkui; Chen, Shan. Delafloxacin intermediate and preparation method thereof. CN 103936717. (Assignee Shanghai Institute of Pharmaceutical Industry, Peop. Rep. China; China State Institute of Pharmaceutical Industry)

• ROUTE 6



Reference: Xiao, Tao; Wang, Xiaoming; Feng, Yi; Tian, Xin; Li, Song. Simple synthesis method of delafloxacin. CN 104876911. (Assignee Nanjing Tech University, Peop. Rep. China)

• ROUTE 7



Reference: Pan, Yuan; Zuo, Xiaoyong; Zhang. Preparation method of highly purified delafloxacin meglumine. CN 106256824. (Assignee Chongqing Pharmaceutical Research Institute Co., Ltd., Peop. Rep. China)

• ROUTE 8



Reference: Zhang, Guimin; Wang, Xiujuan; Zhao, Xuliang; Wu, Suzhen. Method for preparation of delafloxacin. CN 107778293. (Assignee Lunan Pharmaceutical Group Corp., Peop. Rep. China)