Fluorinated Adenosine A2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics

<div>Synthesis of 5a, 5b, and PEGylated analog 40. Conditions: (a) morpholine (33), K3PO4, 2-biphenyl-dicyclohexylphosphine, Pd(OAc)2, dimethoxyethane, 37%; (b) Sn powder, EtOH/con.HCl, 66%; (c) benzoyl isothiocyanate, acetone, 99%; (d) (i) NaOMe, MeOH; (ii) Br2, CHCl3, 73%; (e) phenyl carbonochloridate, pyridine, dichloromethane, 94%; (f) 4-methylpiperidin-4-ol hydrochloride (39), DIPEA, THF, CHCl3, 53%; (g) 26, DIPEA, THF, CHCl3, 28%; (h) BBr3, dichloromethane, 52%; (i) (39), DIPEA, THF, CHCl3, 62%.</div>

International Journal of Medicinal Chemistry

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Scheme 2

Scheme 2: Fluorinated Adenosine A2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics