Method For Preparing Heterocyclic Derivative Compound, Composition Containing Same Compound, And Hydrate of Same Compound

Abstract

The present invention relates to: a novel method for preparing a heterocyclic derivative compound of chemical formula I below; a novel intermediate compound used in the preparation method; a composition for treatment or prevention of hyperuricacidemia, gout, nephritis, chronic renal insufficiency, nephrolith, uremia, urolithiasis, or a uric acid-related disease, the composition containing the compound of chemical formula I at a dose of more than 2 mg and equal to or less than 10 mg and being orally administered once a day; and a hydrochloride 1.5 hydrate of the novel compound of chemical formula I.

1 . A process for preparing a compound of the following Formula I, or a pharmaceutically acceptable salt thereof or a hydrate thereof, comprising coupling-reacting a compound of the following Formula III with a compound of the following Formula IV: 
       
         
           
           
               
               
           
         
         wherein R is hydrogen or tert-butyloxycarbonyl (Boc). 
       
     
     
         2 . The process according to  claim 1 , wherein the compound of Formula III is obtained by reacting a compound of the following Formula II with di-tert-butyl dicarbonate and pyridine: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The process according to  claim 1 , wherein said process comprises the following steps:
 (1) reacting the compound of Formula III with the compound of Formula IV to obtain a compound of Formula V;   (2) reacting the compound of Formula V with an alcohol in the presence of an acid to obtain a salt of the compound of Formula I; and   (3) reacting the salt of the compound of Formula I with a base first and then with an acid secondarily:   
       
         
           
           
               
               
           
         
       
     
     
         4 . The process according to  claim 3 , wherein Steps (1) and (2) are carried out as an in situ reaction. 
     
     
         5 . The process according to  claim 3 , wherein the compound of Formula III is obtained by reacting the compound of Formula II with di-tert-butyl dicarbonate and pyridine: 
       
         
           
           
               
               
           
         
       
       and the above step, and Steps (1) and (2) are carried out as an in situ reaction. 
     
     
         6 . The process according to  claim 1 , wherein the compound of Formula IV is obtained by reacting 3,4-dihydro-2H-pyrido[4,3-b][1,4]oxazine with bromic acid in acetic acid. 
     
     
         7 . A compound of the following Formula III: 
       
         
           
           
               
               
           
         
         wherein R is hydrogen or Boc. 
       
     
     
         8 . A compound of the following Formula IV: 
       
         
           
           
               
               
           
         
       
     
     
         9 . A pharmaceutical composition for the treatment or prevention of hyperuricemia, gout disease, nephritis, chronic renal failure, nephrolithiasis, uremia, urolithiasis, or a disease associated with uric acid, which comprises as an active ingredient a compound of the following Formula I, or a pharmaceutically acceptable salt thereof or a hydrate thereof at a dose of greater than 2 mg to 10 mg or less based on the free base of the compound of Formula I and is orally administered once daily: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the dose is 3 mg to 8 mg. 
     
     
         11 . The pharmaceutical composition according to  claim 9 , wherein the active ingredient is hydrochloride of the compound of Formula I or its 1.5 hydrate (sesquihydrate). 
     
     
         12 . Hydrochloride 1.5 hydrate (sesquihydrate) of the compound of Formula I according to  claim 9 . 
     
     
         13 . The hydrochloride 1.5 hydrate of the compound of Formula I according to  claim 12 , which displays characteristic peaks at the following 2θ (two-theta) positions in the powder X-ray diffraction (XRD) analysis:
   11.48°±0.5°, 24.11°35 0.5°,  24 . 76 °± 0 . 5 °,  27 . 99 °± 0 . 5 °,  31 . 43 °± 0 . 5 °,  34 . 20 °± 0 . 5 °.
 
 
     
     
         14 . The hydrochloride 1.5 hydrate of the compound of Formula I according to  claim 13 , which further displays characteristic peaks at the following 2θ (two-theta) positions in the powder X-ray diffraction (XRD) analysis:
   6.89°±0.5°, 17.61°±0.5°, 21.42°±0.5°, 23.2°±0.5°.
 
 
     
     
         15 . (canceled) 
     
     
         16 . A pharmaceutical composition formulated for oral administration, comprising the hydrochloride 1.5 hydrate of the compound of Formula I according to  claim 12 . 
     
     
         17 . The pharmaceutical composition according to  claim 16 , which is in the form of a tablet.