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

• DOI: 10.1021/acs.oprd.9b00178
• Publication Date: 2019-06-26T17:50:11Z
• Authors: Nastaran Salehi M...; David R. Snead; Jonathan P. McMullen; François Lévesque; Mark Weisel; Richard J. Varsolona; Yu-hong Lam; Zhijian Liu; John R. Naber
• Keywords: 01 natural sciences; 0104 chemical sciences; 3. Good health

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.