One-Step Synthesis of 2-Fluoroadenine Using Hydrogen Fluoride Pyridine in a Continuous Flow Operation

Salehi Marzijarani, Nastaran; Snead, David R.; McMullen, Jonathan P.; Lévesque, François; Weisel, Mark; Varsolona, Richard J.; Lam, Yu-hong; Liu, Zhijian; Naber, John R.

One-Step Synthesis of 2-Fluoroadenine Using Hydrogen Fluoride Pyridine in a Continuous Flow Operation

By Salehi Marzijarani, Nastaran; Snead, David R.; McMullen, Jonathan P.; Lévesque, François; Weisel, Mark; Varsolona, Richard J.; Lam, Yu-hong; Liu, Zhijian; Naber, John R.

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Published on CMKC

23 Jul 2024

Abstract

We report the development of a one-pot synthesis of 2-fluoroadenine from an inexpensive 2,6-diaminopurine starting material using diazonium chemistry in a continuous fashion. Given the sensitivity of this transformation to temperature, we conducted critical experiments to study the exothermicity of the reaction and the heat removal, which were critical for the development of the process. Our goal was to improve the yield and purity of this pharmaceutical intermediate (2-fluoroadenine) and develop a more robust process.

Journal

Organic Process Research & Development. Volume 23, 2019, 1522–1528

DOI

10.1021/acs.oprd.9b00178

Type of publication

Peer-reviewed journal

Affiliations

Merck & Co. Inc.

Article Classification

Research Article

Classification Areas

Intermediate