Development of a Practical Synthesis of the 8-FDC Fragment of OPC-167832

Vijayagopal Gopalsamuthiram; Dang Binh Ho; Cheryl L Peck; Vasudevan Natarajan; Toolika Agrawal; Justina M Burns; John Bachert; Daniel W Cook; Rodger W Stringham; Ryan Nelson; Saeed Ahmad; B Frank Gupton; David R Snead; D Tyler McQuade; Rajappa Vaidyanathan; Kai Donsbach; Joshua D Sieber

doi:10.1021/acsomega.1c06996

Development of a Practical Synthesis of the 8-FDC Fragment of OPC-167832

ACS Omega. 2022 Feb 18;7(8):7223-7228. doi: 10.1021/acsomega.1c06996. eCollection 2022 Mar 1.

Authors

Vijayagopal Gopalsamuthiram¹, Dang Binh Ho^{1

2}, Cheryl L Peck¹, Vasudevan Natarajan¹, Toolika Agrawal^{1

2}, Justina M Burns¹, John Bachert¹, Daniel W Cook¹, Rodger W Stringham¹, Ryan Nelson¹, Saeed Ahmad¹, B Frank Gupton¹, David R Snead¹, D Tyler McQuade¹, Rajappa Vaidyanathan¹, Kai Donsbach¹, Joshua D Sieber^{1

2}

Affiliations

¹ Medicines for All Institute, Virginia Commonwealth University School of Engineering, Chemical Development 737 N 5th Street, Richmond, Virginia 23298-0100, United States.
² Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, Virginia 23284-3208, United States.

Abstract

A concise and practical synthesis has been developed to provide the 8-fluoro-5-hydroxy-3,4-diydrocarbostyril (8-FDC) fragment of OPC-167832 in 41% yield and in >99% purity over four steps from 3-amino-4-fluorophenol. The key feature of this process is the development of a telescoped one-pot synthesis of the quinolone via a chemoselective amidation/acid-induced cyclization that allows for simple product isolation without the need for column chromatography.