Fluorinated Adenosine A_2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics

Scheme 1

Synthesis of 4 and its PEGylated analogs. Conditions: (a) POCl₃, DMF, 78%; (b) 2-furoic acid hydrazide (9), Na₂CO₃, MeCN; (c) 2-hydroxyethyl hydrazine (11), 78% over 2 steps; (d) POCl₃, ZnBr₂, 45%; (e) (i) NaH, DMF; (ii) 6 N HCl. 67% (, 21), 62% (, 22), 56% (, 23), 35% (, 24), 70% (, 25), 70% (, 26); (f) N,N-diisopropylethylamine (DIPEA), DMF, 52% (, 27), 47% (, 28), 33% (, 29), 25% (, 30), 55% (, 4), and 25% (, 31).