A Practical and Efficient Method for the Synthesis of Sorafenib and Regorafenib

A practical syntheses of sorafenib and regorafenib have been achieved in an efficient manner which is free from the problems associated with the methods described in literature. The process involved preparation of 4-(4-aminophenoxy)-N-methylpicolinamide (Sorafenib intermediate) and 4-(4-amino-3-fluorophenoxy)-N-methylpicolinamide (Regorafenib intermediate) using only one base and avoided use of inert atmosphere. The reaction of intermediates with phenyl (4-chloro-3-(trifluoromethyl)phenyl)carbamate - prepared using water-assisted synthesis of carbamates – installed the main urea functionality in these molecules.