Process for the manufacture of 3-hydroxy-n-alkyl-1-cycloalkyl-6-alkyl-4-oxo-1,4-dihydropyridine-2-carboxamide and its related analogues

The present invention relates to a novel process for the preparation of 1-alkyl or 1-cycloalkyl derivatives of 3-hydroxy-4-oxo-1,4-dihydropyridine-2-carboxamide of formula (I). The process includes reacting an amine R2NH2 with a compound of formula (II) in a solution of metal hydroxide in water to give a compound of formula (III). Subsequent reaction of the compound of formula (III) with an acid chloride formation reagent in an inert solvent gives compounds of formula (I). The acid chloride formation reagent is selected from oxalyl chloride and dimethylformamide, dimethyichloromethylene-ammonium chloride and thionyl chloride and dimethylformamide. If desired, a compound of formula (I) where R5 is hydrogen may be formed when an intermediate substituent is used wherein R5 is an alcohol protective group removable by catalytic hydrogenation.