Development of a Commercial Ready Process for TNG908: A Potent, Selective, and Brain-Penetrant MTA-Cooperative PRMT5 Inhibitor

TNG908 is a potent, selective, and brain-penetrant MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted tumors. We describe here the chemical process development for the synthesis of TNG908 and the improvements that were achieved over the medicinal chemistry route with much higher yields and better purities. This commercial ready process is convergent, diastereoselective, safe, reproducible, and robust. A total of eight GMP batches have been successfully manufactured, resulting in high-purity API meeting all specifications.