Patent ID: 7872146
Filing Date: 2011-01-18
Classification: C07D

Abstract:
1. A process for the preparation of a carboxamide derivative of formula (I) or a salt thereof in which: R R A represents an optionally substituted 5-, 6- or 7-membered non-fused heterocycle with one, two or three heteroatoms which may be the same or different, the heterocycle being linked by a carbon atom; said process comprising: (A) a first step according to reaction Scheme 1: in which: R R Hal represents a halogen atom; and Alk represents a C comprising the reaction of a nitrobenzene derivative of formula (II) with a ketoester derivative of formula (III), in a compound (III)/compound (II) molar ratio of from 1 to 10, in a solvent and in the presence of a base, the base/compound (II) molar ratio being of from 0.5 to 5; to provide a nitrophenyl ketoester derivative of formula (IV); (B) a second step according to reaction Scheme 2 in which: R R Alk represents a C R X represents a halogen atom; comprising: (a) in the case R (b) in the case R (C) a third step according to reaction Scheme 3: in which R comprising the reduction of a nitrophenyl ketone of formula (V) obtained in step two by adding to it from 0.5 to 10 molar equivalent of a reduction agent, in a polar protic solvent and at a temperature of from −20° C. to 80° C.; to provide a nitrophenyl alcohol derivative of formula (VI); (D) a fourth step according to reaction Scheme 4: in which R comprising the reduction by H (E) a fifth step according to reaction Scheme 5: in which: A, R Hal represents a halogen atom; comprising the coupling reaction of an aminophenyl alcohol derivative of formula (VII) obtained in step four with an acyl halide derivative of formula (VIII), in a solvent and in the presence of a base in a base/compound (VII) molar ratio of 0.5 to 3; to provide a hydroxycarboxamide derivative of formula (IX); (F) a sixth step according to reaction Scheme 6: in which: A, R p and q are independently chosen as being 1, 2 or 3; R represents a phosphorous atom, —P═O, —S=0, a mesyl group or a tosyl group; X represents a halogen atom; comprising the reaction of a hydroxycarboxamide derivative of formula (IX) obtained in step five with a compound of formula R to provide a carboxamide derivative of formula (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII) or (XVIII), or a mixture thereof; (G) a seventh step according to reaction Scheme 7: in which A, R comprising the reduction by H to provide a carboxamide derivative of formula (I).