A process for preparation of fumarate salt of 9-Ä2-(r)-ÄÄbisÄÄ(isopropoxycarbonyl)oxyÜmethoxyÜphosphinoylÜmethoxyÜpropylÜ-adenine

摘要

The invention provides a composition comprising bis(POC)PMPA and fumaric acid (1:1). The composition is useful as an intermediate for the preparation of antiviral compounds, or is useful for administration to patients for antiviral therapy or prophylaxis. The composition is particularly useful when administered orally. The invention also provides methods to make PMPA and intermediates in PMPA synthesis. Embodiments include lithium t-butoxide, 9-(2-hydroxypropyl) adenine and diethyl p-toluenesulfonylmethoxy-phosphonate in an organic solvent such as DMF. The reaction results in diethyl PMPA preparations containing an improved by-product profile compared to diethyl PMPA made by prior methods.