Selective Synthesis\nof <i>N</i><sup>6</sup>,3′,5′-Tripivaloyladenosine\nvia Dynamic Kinetic Crystallization\nand Regioselective Preparation of Pivalated 2′-Deoxy-2′-fluoroarabinoadenosines

A four chemical step route to 2′-deoxy-2′-fluoro-<i>N</i><sup>6</sup>,3′-dipivaloylarabinoadenosine and 2′-deoxy-2′-fluoro-<i>N</i><sup>6</sup>-pivaloylarabinoadenosine from adenosine was\ndeveloped for the preparation of ulevostinag in our STING (Stimulator\nof Interferon Genes) program. This 4-step route is based on the selective\nprotection of adenosine with a dynamic kinetic crystallization of\nthe desired <i>N</i><sup>6</sup>,3′,5′-tripivaloyladenosine.\nThis is followed by activation of the 2′-alcohol as its triflate\nwithout pivalate migration. Subsequently, the triflate is displaced\nwith fluoride under mild conditions. Selective deprotection of the\nesters can give a variety of mono- and diacylated products including\nthe 3′- or 5′-protected 2′-fluoroarabinonucleoside\nin the presence of the <i>N</i><sup>6</sup>-pivalamide.