US2012010231A1PendingUtilityA1

Dihydroetorphines and Their Preparation

Assignee: WHITELOCK STEVEPriority: Dec 8, 2008Filed: Dec 4, 2009Published: Jan 12, 2012
Est. expiryDec 8, 2028(~2.4 yrs left)· nominal 20-yr term from priority
A61P 25/04A61P 29/00C07D 489/02C07D 489/12A61K 31/485C07D 489/10A61K 9/7023
61
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Claims

Abstract

The present invention provides a process for the preparation of a compound of formula (VI), or a salt or derivative thereof, wherein R 1 and R 2 are independently C 1-8 alkyl and * represents a stereocentre.

Claims

exact text as granted — not AI-modified
1 . A process for the preparation of a compound of formula (VI), or a salt or derivative thereof 
       
         
           
           
               
               
           
         
         (wherein R 1  and R 2  are independently C 1-8  alkyl and * represents a stereocentre) comprising hydrolysing a compound of formula (V) 
       
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and * are as hereinbefore defined. 
       
     
     
         2 . A process as claimed in  claim 1 , wherein said compound of formula (V) is prepared by reacting a compound of formula (IV) 
       
         
           
           
               
               
           
         
         (wherein R 1  is as hereinbefore defined); 
         with a compound of formula R 2 M(X) p , wherein R 2  is C 1-8  alkyl, M is metal, X is halide and p is 1 or O. 
       
     
     
         3 . A process as claimed in  claim 2 , wherein said compound of formula (IV) is prepared by reducing a compound of formula (III) 
       
         
           
           
               
               
           
         
         (wherein R 1  is as hereinbefore defined); 
       
     
     
         4 . A process as claimed in  claim 3 , wherein said compound of formula (III) is prepared by reacting a compound of formula (I) 
       
         
           
           
               
               
           
         
         with a compound of formula (II) 
       
       
         
           
           
               
               
           
         
         (wherein R 1  is C 1-8  alkyl). 
       
     
     
         5 . A process for the preparation of a compound of formula (VI), or a salt or derivative thereof, 
       
         
           
           
               
               
           
         
         (wherein R 1  and R 2  are independently C 1-8  alkyl and * represents a stereocentre) comprising: 
         reacting a compound of formula (I) 
       
       
         
           
           
               
               
           
         
         with a compound of formula (II) 
       
       
         
           
           
               
               
           
         
         (wherein R 1  is C 1-8  alkyl) to give a compound of formula (III) 
       
       
         
           
           
               
               
           
         
         (wherein R 1  is as hereinbefore defined); 
         reducing said compound of formula (III) to produce a compound of formula (IV) 
       
       
         
           
           
               
               
           
         
         (wherein R 1  is as hereinbefore defined); 
         reacting said compound of formula (IV) with a compound of formula R 2 M(X) p , wherein R 2  is C 1-8  alkyl, M is metal, X is halide and p is 1 or 0, to give a compound of formula (V) 
       
       
         
           
           
               
               
           
         
         wherein R 1 , R 2  and * are as hereinbefore defined; 
         (iv) hydrolysing said compound of formula (V) to give a compound of formula (VI). 
       
     
     
         6 . A process as claimed any one of  claims 1  to  5 , further comprising the step of crystallising said compound of formula (VI). 
     
     
         7 . A process as claimed in any one of  claims 1  to  6 , wherein R 1  is propyl. 
     
     
         8 . A process as claimed in any one of  claims 1  to  7 , wherein R 2  is methyl. 
     
     
         9 . A process as claimed in any one of  claims 1  to  8 , wherein the stereocentre (*) in formulae (V) and (VI) is (S). 
     
     
         10 . A process as claimed in any one of  claims 1  to  9 , wherein the compound of formula (V) is: 
       
         
           
           
               
               
           
         
       
     
     
         11 . A process as claimed in any one of  claims 1  to  10 , wherein the compound of formula (VI) is: 
       
         
           
           
               
               
           
         
       
     
     
         12 . A process as claimed in any one of  claims 1  to  8 , wherein the stereocentre (*) in formulae (V) and (VI) is (R). 
     
     
         13 . A compound of formula (VI), or a salt or derivative thereof, 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently C 1-8  alkyl and the * represents a (S) stereocentre. 
       
     
     
         14 . A compound as claimed in  claim 13  of formula (VI) 
       
         
           
           
               
               
           
         
       
     
     
         15 . A compound of formula (V), or a salt or derivative thereof, 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently C 1-8  alkyl and the (*) represents a (S) or (R) stereocentre, preferably a (S) stereocentre. 
       
     
     
         16 . A compound as claimed in  claim 15  of formula (Va) 
       
         
           
           
               
               
           
         
       
     
     
         17 . A compound of formula (IV) 
       
         
           
           
               
               
           
         
         (wherein R 1  is C 1-8  alkyl). 
       
     
     
         18 . A compound of formula (III) 
       
         
           
           
               
               
           
         
         (wherein R 1  is C 1-8  alkyl). 
       
     
     
         19 . A compound as claimed in  claim 17  or  claim 18 , wherein R 1  is propyl. 
     
     
         20 . A process for making a compound of formula (III) comprising reacting a compound of formula (I) 
       
         
           
           
               
               
           
         
         with a compound of formula (II) 
       
       
         
           
           
               
               
           
         
         (wherein R 1  is C 1-8  alkyl) 
       
     
     
         21 . A pharmaceutical composition comprising a compound as claimed in any one of  claims 13  to  19 . 
     
     
         22 . A compound as claimed in any one of  claims 13  to  19  for use in medicine. 
     
     
         23 . A compound as claimed in any one of  claims 13  to  19  for use as an analgesic. 
     
     
         24 . Use of a compound as claimed in any one of  claims 13  to  19  in the manufacture of a medicament for the treatment of pain. 
     
     
         25 . A method of treating a subject in need of pain relief comprising administering to said subject a therapeutically effective amount of a compound as claimed in any one of  claims 13  to  19 .

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