Meanwhile in another presentation from the 4th Winter Process Conference this time from Alexandra Parker of AstraZeneca discussed the development of the manufacturing route to make Lesinurad (Zurampic) a selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with a xanthine oxidase inhibitor (XOI) in patients unable to achieve target serum uric acid (sUA) on a XOI alone.
The final stages are shown in the Scheme below.
Scheme: Synthesis of Lesinurad
Isolation of the sodium salt was tried but the salt is surprisingly low melting (~40°C) and extremely slow to filter, so in the initial manufacturing route all the chemistry from was telescoped, so that neither the brominated methyl ester nor the sodium salt were isolated. An analysis of the throughput revealed that these final stages accounted for 35% of the manufacturing time and this was as a result of the number of washes required. It turned out to be much more efficient to isolate the brominated methyl ester, with a reduction in overall cycle time due to the ability to overlap sequential manufacturing steps.
A. Parker (AstraZeneca) presentation at The 4th Winter Process Conference, Glasgow, December, 2016.