PROCESS FOR PREPARATION OF CYCLIC PRODRUGS OF PMEA AND PMPA

摘要

The method of preparing compounds of Formula I is described: Formula Iwherein:M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmethoxyethyl)adenine, and (R)-9-(2-phosphonylmethoxypropyl)adenine; wherein V is phenyl, optionally substituted with 1-2 substituents selected from a group consisting of fluoro, chloro, and bromo; comprising:coupling a chiral 1-phenylpropane-1,3-diol, wherein the phenyl may be optionally substituted, with MPOCl2 or an N-6 substituted analogue thereof.Additionally, methods and salt forms are described that enable isolation and purification of the desired isomer.