Pyrazole derivative manufacturing method

Abstract

The present invention provides a method for manufacturing a compound represented by formula (I). With this method, provided are a method for manufacturing a 4-heteroaryl-N-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxylic acid amide derivative; and an intermediate for this manufacturing method.

1 . A method for manufacturing a compound represented by formula (AD-2) below: 
       
         
           
           
               
               
           
         
         in formula (AD-2), p denotes an integer between 0 and 3; R 1  groups each independently denote a group arbitrarily selected from among a halogen atom, a cyano group, a C 1-6  alkyl group, a C 3-8  cycloalkyl group, a halogenated C 1-6  alkyl group, a C 2-6  alkenyl group, a C 1-6  alkoxy group, a C 1-6  alkoxy-C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group and a C 2-7  alkanoyl group; R 2  denotes a C 1-6  alkyl group; R 3  denotes a group arbitrarily selected from among a hydrogen atom and a fluorine atom; and ring A group represented by formula (II): 
       
       
         
           
           
               
               
           
         
         denotes a monocyclic 5- to 6-membered heteroaryl group arbitrarily selected from among a thiazol-2-yl group, a thiazol-4-yl group, a 1-methyl-1H-imidazol-4-yl group, a 1,3,4-thiadiazol-2-yl group, a 1,2,4-thiadiazol-5-yl group, a pyridin-2-yl group, a pyridazin-3-yl group, a pyrimidin-2-yl group, a pyrimidin-4-yl group and a pyrazin-2-yl group, the manufacturing method comprising stages in which a compound represented by formula (AD-1): 
       
       
         
           
           
               
               
           
         
         in formula (AD-1), p, R 1 , R 2  and ring A group represented by formula (II) are defined in the same way as for formula (AD-2); and a 2-amino-4-iodopyridine derivative represented by formula (PY-1): 
       
       
         
           
           
               
               
           
         
         in formula (PY-1), R 3  denotes a group arbitrarily selected from among a hydrogen atom and a fluorine atom are reacted with each other using a solvent which does not take part in the reaction and which is selected from the group consisting of 1,4-dioxane, tetrahydrofuran and 1,2-dimethoxyethane at a temperature between 0° C. and a temperature at which the solvent refluxes in the presence of N,N-dimethyl-1,2-ethanediamine, copper iodide and an inorganic base selected from the group consisting of potassium carbonate and potassium phosphate, thereby obtaining the compound represented by formula (AD-2). 
       
     
     
         2 . A method for manufacturing a compound represented by formula (AD-2) below: 
       
         
           
           
               
               
           
         
         in formula (AD-2), p denotes an integer between 0 and 3; R 1  groups each independently denote a group arbitrarily selected from among a halogen atom, a cyano group, a C 1-6  alkyl group, a C 3-8  cycloalkyl group, a halogenated C 1-6  alkyl group, a C 2-6  alkenyl group, a C 1-6  alkoxy group, a C 1-6  alkoxy-C 2-6  alkyl group, a hydroxy-C 1-6  alkyl group and a C 2-7  alkanoyl group; R 2  denotes a C 1-6  alkyl group; R 3  denotes a group arbitrarily selected from among a hydrogen atom and a fluorine atom; and ring A group represented by formula (II): 
       
       
         
           
           
               
               
           
         
         denotes a monocyclic 5- to 6-membered heteroaryl group arbitrarily selected from among a thiazol-2-yl group, a thiazol-4-yl group, a 1-methyl-1H-imidazol-4-yl group, a 1,3,4-thiadiazol-2-yl group, a 1,2,4-thiadiazol-5-yl group, a pyridin-2-yl group, a pyridazin-3-yl group, a pyrimidin-2-yl group, a pyrimidin-4-yl group and a pyrazin-2-yl group, the manufacturing method comprising stages in which a compound represented by formula (ET-1): 
       
       
         
           
           
               
               
           
         
         in formula (ET-1), p, R 1 , R 2  and ring A group represented by formula (II) are defined in the same way as for formula (AD-2); R D  denotes a group arbitrarily selected from among a C 1-6  alkyl group, a C 6-14  aryl group and a C 7-20  aralkyl group; and an aqueous ammonia solution are reacted with each other at a temperature between 0° C. and a temperature at which the reaction solution refluxes, thereby obtaining a compound represented by formula (AD-1): 
       
       
         
           
           
               
               
           
         
         in formula (AD-1), p, R 1 , R 2  and ring A group represented by formula (II) are defined in the same way as for formula (AD-2), and the compound represented by formula (AD-1) and a 2-amino-4-iodopyridine derivative represented by formula (PY-1): 
       
       
         
           
           
               
               
           
         
         in formula (PY-1), R 3  denotes a group arbitrarily selected from among a hydrogen atom and a fluorine atom are reacted with each other using a solvent which does not take part in the reaction and which is selected from the group consisting of 1,4-dioxane, tetrahydrofuran and 1,2-dimethoxyethane at a temperature between 0° C. and a temperature at which the solvent refluxes in the presence of N,N-dimethyl-1,2-ethanediamine, copper iodide and an inorganic base selected from the group consisting of potassium carbonate and potassium phosphate, thereby obtaining the compound represented by formula (AD-2). 
       
     
     
         3 . A compound represented by formula (AD-1) below: 
       
         
           
           
               
               
           
         
         in formula (AD-1), p denotes an integer between 0 and 3; R 1  groups each independently denote a group arbitrarily selected from among a halogen atom, a cyano group, a C 1-6 alkyl group, a C 3-8  cycloalkyl group, a halogenated C 1-6 alkyl group, a C 2-6  alkenyl group, a C 1-6  alkoxy group, a C 1-6  alkoxy-C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group and a C 2-7  alkanoyl group; R 2  denotes a C 1-6  alkyl group; and ring A group represented by formula (II): 
       
       
         
           
           
               
               
           
         
         denotes a monocyclic 5- to 6-membered heteroaryl group arbitrarily selected from among a thiazol-2-yl group, a thiazol-4-yl group, a 1-methyl-1H-imidazol-4-yl group, a 1,3,4-thiadiazol-2-yl group, a 1,2,4-thiadiazol-5-yl group, a pyridin-2-yl group, a pyridazin-3-yl group, a pyrimidin-2-yl group, a pyrimidin-4-yl group and a pyrazin-2-yl group, or a salt of the compound, or a solvate of the compound or salt. 
       
     
     
         4 . The compound of  claim 3 , wherein the compound is any one of intermediate compounds below, or a salt of the intermediate compound, or a solvate of the intermediate compound or salt:
 4-(2,5-dimethylpyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxamide;   1-methyl-4-(2-methylpyrimidin-4-yl)-1H-pyrazole-5-carboxamide;   4-(5-fluoro-2-methoxypyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxamide; and   1-methyl-4-(4-(trifluoromethyl)thiazol-2-yl)-1H-pyrazole-5-carboxamide.   
     
     
         5 . A compound represented by formula (AD-2) below: 
       
         
           
           
               
               
           
         
         in formula (AD-2), p denotes an integer between 0 and 3; R 1  groups each independently denote a group arbitrarily selected from among a halogen atom, a cyano group, a C 1-6  alkyl group, a C 3-8  cycloalkyl group, a halogenated C 1-6  alkyl group, a C 2-6  alkenyl group, a C 1-6  alkoxy group, a C 1-6  alkoxy-C 1-6  alkyl group, a hydroxy-C 1-6  alkyl group and a C 2-7  alkanoyl group; R 2  denotes a C 1-6  alkyl group; R 3  denotes a group arbitrarily selected from among a hydrogen atom and a fluorine atom; and ring A group represented by formula (II): 
       
       
         
           
           
               
               
           
         
         denotes a monocyclic 5- to 6-membered heteroaryl group arbitrarily selected from among a thiazol-2-yl group, a thiazol-4-yl group, a 1-methyl-1H-imidazol-4-yl group, a 1,3,4-thiadiazol-2-yl group, a 1,2,4-thiadiazol-5-yl group, a pyridin-2-yl group, a pyridazin-3-yl group, a pyrimidin-2-yl group, a pyrimidin-4-yl group and a pyrazin-2-yl group, or a salt of the compound, or a solvate of the compound or salt. 
       
     
     
         6 . The compound of  claim 5 , wherein the compound is any one of intermediate compounds below, or a salt of the intermediate compound, or a solvate of the intermediate compound or salt:
 N-(2-amino-5-fluoropyridin-4-yl)-4-(2,5-dimethylpyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxamide;   N-(2-amino-5-fluoropyridin-4-yl)-4-(2-methylpyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxamide; and   N-(2-amino-5-fluoropyridin-4-yl)-4-(5-fluoro-2-methoxypyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxamide;   N-(2-amino-5-fluoropyridin-4-yl)-4-(4-(trifluoromethyl)thiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxamide.