Direct chlorination of adenosine 3',5'-cyclic phosphate (I) was carried out by treatment with anhydrous HCl and m-chloroperbenzoic acid (m-CPBA) in DMF or with N-chlorosuccinimide and NaCl in aqueous HOAc. Chlorination of adenosine (II) was achieved by treatment with HCl in the presence of m-CPBA or in the absence of the oxidating reagent m-CPBA at a higher temperature and longer reaction times. The resultant 8-chloroadenosine (III) was converted to the monophosphate (IV) by means of POCl3, and this was further cyclized to the title compound using DCC. 8-Chloroadenosine monophosphate (IV) was also accessible by chlorination of adenosine monophosphate (V). Optionally, the chlorinated adenosine (III) was directly converted to the title cyclic phosphate by phosphorylation with POCl3 in the presence of NaOH in triethyl phosphate as the solvent.
The title chloro derivative was also obtained by halogen exchange of the previously reported 8-bromoadenosine cyclic phosphate (VI) with CaCl2 in hot DMF. Alternatively, the 8-thioadenosine derivative (VII) was converted into the target compound by treatment with elemental chlorine in methanolic HCl at -15 C.