Scheme 1.

Synthesis of ProTide-Based 2-PMPA Prodrug 9.a
aReagents and conditions: (a) HP(O)(OBn)2, DBU, rt; (b) H2, Pd/C, EtOH; (c) (i) SOCl2/DMF, sulfolane, 70 °C; (ii) PhO-SiMe3, 90 °C; (d) SOCl2, ACN, 70 °C; (e) L-alanine isopropyl ester, DIEA, DCM, between −10 to −30 °C.