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

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

Vijayagopal Gopalsamuthiram  1 , Dang Binh Ho  1   2 , Cheryl L Peck  1 , Vasudevan Natarajan  1 , Toolika Agrawal  1   2 , Justina M Burns  1 , John Bachert  1 , Daniel W Cook  1 , Rodger W Stringham  1 , Ryan Nelson  1 , Saeed Ahmad  1 , B Frank Gupton  1 , David R Snead  1 , D Tyler McQuade  1 , Rajappa Vaidyanathan  1 , Kai Donsbach  1 , Joshua D Sieber  1   2
Affiliations

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

Vijayagopal Gopalsamuthiram et al. ACS Omega. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
OPC-167832.
Scheme 1
Scheme 1. Reported and Proposed Synthetic Strategy to 8-FDC
Scheme 2
Scheme 2. Planned Forward Synthesis of 8-FDC
Figure 2
Figure 2
Mass recovery vs sulfuric acid loading and solvent.
Scheme 3
Scheme 3. Telescoped One-Pot Quinolone Synthesis
Figure 3
Figure 3
Reaction progress at different stages utilizing reverse-quenching. (a) Reaction of 10, PivCl, and DIPEA. (b) After addition of 6, rt, 14 h. (c) After addition of H2SO4. (d) After inverse quench. (e) Filtered product.
Scheme 4
Scheme 4. Conversion of Quinolone 7 to 8-FDC
See this image and copyright information in PMC

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