Process for preparation of cabozantinib

A process for the preparation of N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N′-(4-Fluorophenyl) cyclopropane-1,1-dicarboxamide (compound of Formula II) or its malate salt (of Formula I) comprising the following steps:

• a) activating 1-(4-Fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (compound of Formula V) using a suitable sulfonyl chloride, optionally in presence of a suitable base in a suitable solvent,
• b) adding 4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline (compound of Formula III),
• c) isolating N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N′-(4-Fluorophenyl) cyclopropane-1,1-dicarboxamide (compound of Formula II), and
• d) optionally converting N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N′-(4-Fluorophenyl) cyclopropane-1,1-dicarboxamide (compound of Formula II) to its malate salt (of Formula I);
• or
• a′) adding a suitable sulfonate chloride to a solution of 1-(4-Fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (compound of Formula V) and 4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline (compound of Formula III) in a suitable solvent,
• b′) isolating N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N′-(4Fluorophenyl) cyclopropane-1,1-dicarboxamide (compound of Formula II);
• and
• c′) optionally converting N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N′-(4-Fluorophenyl) cyclopropane-1,1-dicarboxamide (compound Formula II) to its malate salt (of Formula I).