Patent ID: 7276611
Filing Date: 2007-10-02
Classification: A61P,C07D

Abstract:
1. A process for the preparation of bicyclic heteroaryl carboxaldehydes of Formula I wherein: Y is (CH n is 1 or 2; X is CH which process comprises the steps of: a. nitrosating an amino acid 1 of the formula wherein X and Y are defined as above with a nitrosating reagent to form a nitroso compound of formula 2 wherein X and Y are defined as above b. reacting the nitroso compound 2 with a dehydrating agent and neutralizing with an inorganic base to form the ylide of formula 3 wherein X and Y are defined as above c. reacting the ylide of formula 3 with a propiolate ester of formula 4 where R 1 is alkyl of 1 to 6 carbon atoms, in aprotic solvents to form a mixture of bicyclic-heteroaryl-3-carboxylate ester of formula 5 and bicyclic-heteroaryl-2-carboxylate ester of formula 6 wherein R 1 , X and Y are defined as above d. reacting the mixture of bicyclic-heteroaryl-3-carboxylate ester 5 and bicyclic-heteroaryl-2-carboxylate ester 6 with a hydrolyzing reagent MOR e. isolating the salt 7; f. reacting the salt 7 with acid to form bicyclic-heteroaryl-2-carboxylic acid 8 of formula wherein X and Y are defined as above g. reacting the bicyclic-heteroaryl-2-carboxylic acid 8 or salts thereof with an acid halide reagent or coupling reagent to form an activated intermediate of formula 9 where Q is a leaving group formed from the coupling reagent or acid halide reagent wherein X and Y are defined as above h. reacting an activated intermediate of formula 9 or the bicyclic-heteroaryl carboxylic acid 8 with a substituted hydroxylamine of the formula R i. reducing the amide of formula 11 with a reducing agent to provide a bicyclic heteroaryl carboxaldehyde of Formula I wherein X and Y are defined as above and isolating the heteroaryl carboxaldehyde of Formula I.