Process development of a disease-modifying antirheumatic drug, TAK-603, based on optimization of Friedel-Crafts reaction and selective substitution of a triazole ring

A practical method for the preparation of TAK-603, an antirheumatic drug, has been developed. As a result of optimizing the Friedel-Crafts reaction in the presence of SnCl4/POCl3, 2-aminobenzophenone skeleton, the key intermediate of TAK-603, was formed with Pod yield. The selective substitution reaction of 1,2,4-triazole was accomplished using 4-amino-1,2,4-triazole and deamination. (c) 2006 Elsevier Ltd. All rights reserved.