Patent ID: 9012645
Filing Date: 2015-04-21
Classification: C07C,C07D,Y02P

Abstract:
1. Process for the preparation of the compound 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide of formula (I): or a pharmaceutically acceptable salt thereof, comprising the following steps: a) reacting an 1-amino-1-hydroxymethylcyclopropane protected at the amino group of formula (VI): wherein R and R′ taken together with the nitrogen atom they are linked to represent a protected primary amino group, with 4-hydroxy-3-methoxyacetophenone of formula (VII): in the conditions of the Mitsunobu reaction, to obtain a compound of formula (VIII): wherein R and R′ are as defined above; b) nitrating a compound of formula (VIII) to obtain a compound of formula (IX): wherein R and R′ are as defined above; c) reacting a compound of formula (IX) with a compound of formula (XV): HC(OR1) wherein R1 is straight or branched C wherein R and R′ are as defined above and the line d) reducing the nitro group of a compound of formula (X) and concomitantly cyclizing to obtain a compound of formula (XI) which can be in equilibrium with its tautomeric form (XIa): wherein R and R′ are as defined above; e) converting a compound of formula (XI) or (XIa) to a compound of formula (XII): wherein X is selected from Cl, Br or I and R and R′ are as defined above; f) reacting a compound of formula (XII) with 6-hydroxy-N-methyl-1-naphthamide of formula (XIII): to obtain a compound of formula (XIV): wherein R and R′ are as defined above; g) deprotecting the protected primary amino group of a compound of formula (XIV) to obtain the compound of formula (I); h) optionally converting the compound (I) in a pharmaceutically acceptable salt thereof.