PMPA, (9-[9(R)-2-(phosphonomethoxy)propyl]adenine



A two-step preparation of (R)-(((1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonic acid (PMPA) from high volume, low-cost raw materials is described. A simple process affords the phosphonic acid intermediate that can be converted into either tenofovir disoproxil fumarate or tenofovir alafenamide fumarate. M4All’s process avoids N-alkylation issues and improves the processability of the synthesis. M4All’s synthesis has a lower number of unit operations, reduced processing time and a lower waste-to-drug mass ratio when compared to typical manufacturing processes for PMPA.