US2017253577A1PendingUtilityA1

Method for producing indole compound

Assignee: JAPAN TOBACCO INCPriority: Jul 4, 2014Filed: Jul 3, 2015Published: Sep 7, 2017
Est. expiryJul 4, 2034(~7.9 yrs left)· nominal 20-yr term from priority
A61P 29/00C07D 405/04C07D 405/14C07D 231/56C07C 269/00C07D 403/04C07C 271/28A61K 31/5377
40
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Claims

Abstract

The present invention aims to provide a new method for producing an indole compound or a salt thereof, which has an ITK inhibitory action, and is useful for the prophylaxis or treatment of inflammatory disease. The present invention is a method for producing N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-(2S)-2-(morpholin-4-yl)propanamide, which comprises a step of reacting

Claims

exact text as granted — not AI-modified
1 . A method of producing a compound of the formula [I] 
       
         
           
           
               
               
           
         
         which comprises a step of removing the protecting group from a compound of the formula [III] 
       
       
         
           
           
               
               
           
         
       
       to give a compound of the formula [I]. 
     
     
         2 . A method of producing a compound of the formula [II] 
       
         
           
           
               
               
           
         
         which comprises a step of treating a compound of the formula [I] 
       
       
         
           
           
               
               
           
         
       
       with hydrogen chloride to give a compound of the formula [II]. 
     
     
         3 . A method of producing a compound of the formula [II] 
       
         
           
           
               
               
           
         
         which comprises a step of removing the protecting group from a compound of the formula [III] 
       
       
         
           
           
               
               
           
         
       
       to give a compound of the formula [I], and
 a step of treating a compound of the formula [I] 
 
       
         
           
           
               
               
           
         
       
       with hydrogen chloride to give a compound of the formula [II]. 
     
     
         4 . The method of  claim 1  or  3 , which further comprises a step of reacting a compound of the formula [V] 
       
         
           
           
               
               
           
         
         with a compound of the formula [IV] 
       
       
         
           
           
               
               
           
         
         or a reactive derivative thereof or a salt thereof to give a compound of the formula [III] 
       
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 4 , which further comprises a step of subjecting a compound of the formula [VI] 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are each independently hydrogen, C 1-6  alkyl or C 1-6  alkoxy, 
       
       to a reduction reaction to give a compound of the formula [V] 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 5 , which further comprises a step of reacting a compound of the formula [VII] 
       
         
           
           
               
               
           
         
         with a compound of the formula [XI] 
       
       
         
           
           
               
               
           
         
         to give a compound of the formula [VI] 
       
       
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 6 , which further comprises a step of subjecting a compound of the formula [VIII] 
       
         
           
           
               
               
           
         
         to tetrahydropyranylation to give a compound of the formula [VII] 
       
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 7 , which further comprises a step of reacting a compound of the formula [IX] 
       
         
           
           
               
               
           
         
         with a compound of the formula [X] 
       
       
         
           
           
               
               
           
         
         wherein
 M is sodium or potassium, 
 
         to give a compound of the formula [VIII] 
       
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 2  or  3 , which further comprises a step of purifying a compound of the formula [II] 
       
         
           
           
               
               
           
         
         with 1-propanol. 
       
     
     
         10 . (canceled) 
     
     
         11 . A compound of the formula [V] 
       
         
           
           
               
               
           
         
       
     
     
         12 . A compound of the formula [III] 
       
         
           
           
               
               
           
         
       
     
     
         13 . A compound of the formula [VI] 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are each independently hydrogen, C 1-6  alkyl or C 1-6  alkoxy. 
       
     
     
         14 . A compound of the formula [VII] 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, C 1-6  alkyl or C 1-6  alkoxy. 
       
     
     
         15 . A compound of the formula [VIII] 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, C 1-6  alkyl or C 1-6  alkoxy. 
       
     
     
         16 . A compound of the formula [XI] 
       
         
           
           
               
               
           
         
         wherein R 2  is hydrogen, C 1-6  alkyl or C 1-6  alkoxy.

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