Patent ID: 7560565
Filing Date: 2009-07-14
Classification: A61P,C07D

Abstract:
1. A process for preparing a 3-hydroxypicolinic acid derivative compound of formula (I): wherein: n represents 0 or 1, Q Q Q Z is selected from the group consisting of a hydrogen atom, a cyano radical and an alkyl, allyl, aryl, arylalkyl, propargyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, cyanoalkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, alkylthioalkyl, haloalkylthioalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, acylaminoalkyl, alkoxycarbonylaminoalkyl, aminocarbonylaminoalkyl, alkoxycarbonyl, N-alkylaminocarbonyl, N,N-dialkylaminocarbonyl, acyl, thioacyl, alkoxythiocarbonyl, N-alkylaminothiocarbonyl, N,N-dialkylaminothiocarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxysulfonyl, aminosulfonyl, N-alkylaminosulfonyl, N,N-dialkylaminosulfonyl, arylsulfinyl, arylsulfonyl, aryloxysulfonyl, N-arylaminosulfonyl, N,N-diarylaminosulfonyl and an N,N-arylalkylaminosulfonyl radical; Y is selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl, mercapto, nitro, thiocyanato, azido, cyano or pentafluorosulfonyl radical, an alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkoxyalkyl, haloalkoxyalkyl, alkylthioalkyl, haloalkylthioalkyl, cyanoalkyl, cyanoalkoxy, cyanoalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl or alkoxysulfonyl radical, a cycloalkyl, halocycloalkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, alkenylthio or alkynylthio group, an amino, N-alkylamino, N,N-dialkylamino, —NHCOR X X R R R T represents a direct bond or a divalent radical chosen from a radical —(CH R R as well as the optional N-oxides, geometrical and/or optical isomers, enantiomers and/or diastereoisomers, tautomeric forms, their salts or metal or metalloid complexes, wherein said process comprises reacting a compound of formula (II)  with a cyanide, alkali metal derivatives or alkaline-earth metal derivatives of hydrocyanic acid in the presence of an alkylating agent and a solvent, or with trimethylsilyl cyanide in the presence of dimethylcarbamoyl chloride and a solvent, to give a compound of formula (III) the compound of formula (III) above can be converted into a corresponding halo derivative of formula (IVa):  wherein X represents a halogen atom selected from the group consisting of fluorine, chlorine, bromine and iodine, by reaction with an acyl halide in the presence of a solvent, the halo derivative of formula (IVa) then being hydrolyzed to a compound of formula (Ia):  by the action of hot hydracid—or of a strong mineral base, optionally in the presence of aqueous hydrogen peroxide solution—and optionally of boron tribromide, the compounds of formula (III) or (IVa) can then optionally be placed in contact with an alcohol or an alkoxide in the presence of a solvent to give a compound of formula (IVb):  that is then hydrolyzed under operating conditions similar to those used for the formation of the compounds of formula (Ia), to give the compounds of respective formulae (Ib) and (Ib′) the compound of formula (IVa) can alternatively be converted into a picolinic acid derivative of formula (Va): by reacting a compound of formula R the nitrile of formula (Va) then being hydrolyzed to give the corresponding acid of formula (Ic):  according to a reaction similar to that used to form the compound of formula (Ia), the halides of formula (IVa) can also optionally be treated with an azothydric acid salt at a temperature of between 0° C. and the boiling point of the solvent, to give the compound of formula (Vb): the compound of formula (Vb) can then optionally be hydrolyzed according to techniques similar to those presented for the preparation of the acids of formula (Ia) above, to give the acid of formula (Id):  the azides of formula (Id) then being optionally reduced to an amine derivative of formula (Ie):  by the action of a reducing agent, the acids of formulae (Ia) to (Ie) can optionally be converted into thio acids, imino derivatives (—C(═NR the acids (Ia) to (Ie), or the thio, imino and imino-amino derivatives thereof defined above, substituted in position 3 (relative to the pyridine nitrogen atom) with —OH or -methoxy can optionally be subjected to various reactions known in the art to give the corresponding derivatives substituted in position 3 (relative to the pyridine nitrogen atom) with —O—Z, the compound of formula (I) wherein Y represents an amino radical (—NH the picolinic acid derivative of formula (VII):  can optionally be placed in contact with a reagent of formula R  which are special cases of the compound of formula (I) in which Q the compounds of general formula (IX):  which are special cases of the compound of formula (I) for which n is equal to 1, can optionally be obtained by a process comprising placing a compound of formula (X):  which is a special case of the compounds of formula (I) for which n is equal to zero, in contact with an oxidizing agent, aqueous hydrogen peroxide solution or carboxylic, boronic or sulfuric peracids.