Patent ID: 7396835
Filing Date: 2008-07-08
Classification: A61P,C07D

Abstract:
1. A process for the preparation of a 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt and as a hydrated salt having the structural formula (I) wherein: R R n is an integer of 2, 3, or 4; X is Cl or Br; R R R which process comprises: a. reacting a malonic acid ester of the formula where R 6 and R 7 are independently C 1 -C 3 alkyl with 3-amino-1,2,4-triazole, in the presence of trialkyl amine base and heating at about 130-170° C., for about 1 to 6 h, cooling to about 130° C., diluting with toluene, cooling to about 20° C. to about 30° C., and adding at least two equivalents of aqueous alkali metal hydroxide (MOH) and isolating the dimetal salt of the formula b. halogenating the dimetal salt with a halogenating reagent POX c. reacting the halogenated product with an amine in an aprotic solvent at about 20° C. to about 30° C. to obtain the amine product of the formula d. reacting an alkali metal hydride with an aminoalcohol HO—(CH e. reacting the 6-[(substituted)phenyl]-triazolopyrimidine product in water with a dicarboxylic acid of the formula wherein the dashed line is an optional bond and adding a solvent selected from t-butylmethyl ether, ethyl acetate and toluene to obtain the 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt as a solid f. crystallizing the 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt from water and collecting the 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt; g. forming the anhydrous 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt by drying the 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt; and h. treating the anhydrous 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt with water to obtain a 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt of formula (I) as a hydrated salt