Synthesis of 3′-deoxyadenosine-5′-O-[phenyl(benzyloxy-L-alaninyl)]phosphate (NUC-738)

A process for the preparation of NUC-7738 (I)

• the process comprising steps b), c), d), e) and f):
• b) treating a compound of formula (VI) with a hydride reducing agent to provide a compound of formula (V)
• c) introducing the protecting group P2 onto the 2′ hydroxy group of a compound of formula (V) to provide a compound of formula (II)
• d) removing the protecting group P1 from a compound of formula (II) to provide 2′-protected Cordycepin (I)
• wherein P1 and P2 are silyl protecting groups and P3 and P4 are each independently selected from H and a protecting group;
• e) converting the compound of formula (I) into a compound of formula (IV)
• (IV);
• and
• f) removing protecting group P2 and, where P3 and P4 are protecting groups, removing P3 and P4 to provide NUC-7738;
• wherein the overall yield of steps b), c), and d) is 70%-100%.