The optimization of chemical processes in the pharmaceutical industry is very important for both the reduction of costs and environmental protection. The more simple the solutions found, the more successful the process. Also there are cases where Topharman has had to discover pathways so as not to infringe upon existing patents.

In the process development of telmisartan, Topharman chemists found that the methyl ester form of 4'-(bromomethyl)-biphenyl-2-carboxylic acid, is more easily manufactured than the t-butyl ester form (V.EP 502314), and is cost-efficient. Also the methyl group in IIIa can be readily removed in the final step (CN 01126367.9 ).

In another patent of the telmisartan process (CN 01131915.1), we found the possibility of directly linking III with Vb, a much cheaper material than Va, led to our success in finding the most cost efficient route to telmisartan:

A young Topharman chemist found a facile way to candesartan cilexetil (CN 00135191.5), enabling the activity of the non-infringing process:

Note: Below is the patented route of candesartan cilexetil (EP 459136, eidemUS 5196444):