US2011097269A1PendingUtilityA1

Phenyloxyaniline derivatives

38
Assignee: LEHMANN LUTZPriority: Sep 4, 2006Filed: Nov 12, 2010Published: Apr 28, 2011
Est. expirySep 4, 2026(~0.1 yrs left)· nominal 20-yr term from priority
C07F 7/1804A61K 51/04C07C 2601/14C07C 233/88C07C 309/66C07D 309/12A61K 49/04C07F 7/18C07C 309/69
38
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Claims

Abstract

The present invention relates to phenyloxyaniline derivatives, to methods of their production and to uses thereof.

Claims

exact text as granted — not AI-modified
1 - 6 . (canceled) 
     
     
         7 . A compound of formula II: 
       
         
           
           
               
               
           
         
         wherein 
         A is
 a) hydrogen 
 b) SiR 1   3    
 c) CH 2 -G 
 d) C(O)-Q 
 e) C(O)O-E 
 f) —(R 2 -phenyl) 
 g) —((R 2 )-2-phenyl) 
 h) tetrahydropyranyl 
 i) (1-alkoxy)-alkyl 
 j) (1-alkoxy)-cycloalkyl 
 k) allyl or 
 l) tert-butyl, 
 
         wherein G is
 a) phenyl 
 b) alkoxy 
 c) dimethoxyphenyl 
 d) nitrophenyl 
 e) halophenyl 
 f) di-halophenyl 
 g) cyanophenyl 
 h) p-biphenyl 
 i) acylaminophenyl 
 j) triphenyl 
 k) (methoxyphenyl)phenyl 
 l) di(methoxyphenyl)phenyl 
 m) -naphtyldiphenyl, or 
 n) hydrogen 
 
         and Q is
 a) hydrogen 
 b) C 1 -C 5  branched and unbranched alkyl 
 c) halomethyl 
 d) dihalomethyl 
 e) trihalomethyl 
 f) phenyl 
 g) biphenyl 
 h) triphenylmethoxymethyl and or 
 i) phenoxymethyl, 
 
         and E is
 a) lower branched and unbranched alkyl 
 b) methoxymethyl 
 c) vinyl 
 d) allyl 
 e) benzyl 
 f) methoxyphenyl 
 g) dimethoxyphenyl or 
 h) nitrophenyl, 
 
         and wherein R 1  is
 a) lower branched and unbranched alkyl, 
 b) phenyl, or 
 c) benzyl, 
 
         and wherein R 2  is
 a) methoxy, 
 b) nitro, 
 c) halo, or 
 d) cyano. 
 
       
     
     
         8 . The compound according to  claim 7 , wherein A is
 a) hydrogen   b) SiR 1   3      c) CH 2 -G   d) tetrahydropyranyl   e) allyl or   f) tert-butyl.   
     
     
         9 . The compound according to  claim 8 , wherein A is
 a) hydrogen   b) SiR 1   3      c) CH 2 -G   d) tetrahydropyranyl, or   e) tert-butyl.   
     
     
         10 . The compound according to  claim 7 , wherein G is
 a) phenyl   b) methoxy   c) p-methoxyphenyl   d) p-nitrophenyl   e) p-chlorophenyl, or   f) triphenyl.   
     
     
         11 . The compound according to  claim 9 , wherein G is
 a) phenyl,   b) methoxy, or   c) p-methoxyphenyl.   
     
     
         12 . The compound according to  claim 7 , wherein Q is
 a) hydrogen   b) methyl   c) phenyl, or   d) phenoxymethyl.   
     
     
         13 . The compound according to  claim 12 , wherein Q is
 a) methyl, or   b) phenyl.   
     
     
         14 . The compound according to  claim 7 , wherein E is
 a) methyl   b) tert-butyl   c) methoxymethyl, or   d) phenyl   
     
     
         15 . The compound according to  claim 14 , wherein E is
 a) methyl   c) tert-butyl, or   b) phenyl   
     
     
         16 . The compound according to  claim 7 , wherein R 1  is
 a) methyl   b) ethyl   c) isopropyl   d) tert-butyl   e) phenyl, or   f) benzyl.   
     
     
         17 . The compound according to  claim 16 , wherein R 1  is
 a) methyl   b) ethyl   c) isopropyl   d) tert-butyl, or   e) phenyl.   
     
     
         18 . The compound according to  claim 7 , wherein R 2  is
 a) methoxy   b) nitro, or   c) chloro.   
     
     
         19 . The compound according to  claim 18 , wherein R 2    a) methoxy, or   b) nitro.   
     
     
         20 . The compound according to  claim 7 , that is 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         21 . A process for preparing a compound of formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R is
   —OS(O) 2 -L
 
 
         and wherein L is
 a) methyl 
 b) trifluormethyl 
 c) nonafluorobutyl 
 d) C 1 -C 6  alkyl-phenyl 
 e) (2,4,6-C 1 -C 6 tri-alkyl)-phenyl 
 f) nitro-phenyl or 
 g) halo-phenyl 
 
         or a compound of formula I wherein L is (para-methyl)-phenyl, comprising: 
         a) reductively N-alkylating a compound of formula III: 
       
       
         
           
           
               
               
           
         
         
           with an aldehyde of formula IV 
         
       
       
         
           
           
               
               
           
         
         and subsequent N-acetylation, or 
         b) N-alkylating an aniline of formula V: 
       
       
         
           
           
               
               
           
         
         
           with an electrophile of formula VI 
         
       
       
         
           
           
               
               
           
         
         and subsequent N-acetylation, or 
         c) alkylation of phenol 4 with an 
       
       
         
           
           
               
               
           
         
         
           electrophile of formula VII 
         
       
       
         
           
           
               
               
           
         
         d) N-alkylating of the compound of formula VIII 
       
       
         
           
           
               
               
           
         
         with an electrophile of formula VI 
         wherein 
         X is a) nitro or
 b) amino, 
 and 
 
         Z is, independently,
 a) R, 
 b) tosyloxy, or 
 c) O-A, and 
 
         wherein R 3  is independently
 a) R, or 
 b) tosyloxy. 
 
       
     
     
         22 . The process according to  claim 21 , wherein Z is
 a) methanesulphonyloxy   b) trifluoromethansulphonyloxy   c) nonafluorobutanesulfonyloxy   d) tosyloxy   e) bromo, or   f) O-A.   
     
     
         23 . The process according to  claim 22 , wherein Z is
 a) methanesulphonyloxy   b) trifluoromethansulphonyloxy   c) nonafluorobutanesulfonyloxy   d) tosyloxy   e) bromo   f) hydroxyl   g) (tert-butyl dimethyl)silyloxy   h) (triisopropyl)silyloxy   ii) phenyl-methyl)oxy   jj) (2-tetrahydropyranyl)oxy I, or   kk) tert-butyloxy.   
     
     
         24 . The process according to  claim 21 , wherein
 R 3  is
 a) R. 
   
     
     
         25 .- 29 . (canceled) 
     
     
         30 . A kit comprising a sealed vial containing a compound according to  claim 7  wherein, said sealed vial contains a predetermined quantity of said compound. 
     
     
         31 . (canceled) 
     
     
         32 . A method diagnostic imaging comprising administering a diagnostically effective amount of a diagnostic imaging agent comprising a compound according to  claim 7 . 
     
     
         33 . A method according to  claim 32 , wherein said diagnostic imaging agent is far administered to image diseases of the central nervous system. 
     
     
         34 . A process of preparing compound 3 
       
         
           
           
               
               
           
         
         comprising 
         a) reacting compound 7 
       
       
         
           
           
               
               
           
         
         with  18 F anions, 
         at temperatures in the range of from 121° C. to 160° C., and, optionally, upon obtainment of compound 3, adding acid. 
       
     
     
         35 . The process of preparing compound 3 
       
         
           
           
               
               
           
         
         comprising 
         reacting a compound of formula I, 
       
       
         
           
           
               
               
           
         
         wherein 
         R is —OS(O) 2 -L 
         and wherein L is
 a) methyl 
 b) trifluormethyl 
 c) nonafluorobutyl 
 d) C 1 -C 6  alkyl-phenyl 
 e) (2,4,6-C 1 -C 6  tri-alkyl)-phenyl 
 f) nitro-phenyl or 
 g) halo-phenyl 
 with the proviso that L is not (para-methyl)-phenyl. 
 
         with  18 F anions at temperatures in the range of from 75° C. to 150° C. 
       
     
     
         36 . The process according to  claim 35 , wherein said temperatures are in the range of from 85° C. to 140° C. 
     
     
         37 . The process according to  claim 34 ,
 comprising reacting compound 7 with  18 F anions at temperatures in the range of from 121° C. to 150° C., and, optionally, upon obtainment of compound 3, adding at least one mineral acid having a concentration in the range of from 0.5N-6N.   
     
     
         38 . The process according to  claim 34 ,
 comprising reacting compound 7 with  18 F anions, at temperatures in the range of from 121° C. to 140° C., and, optionally upon obtainment of compound 3, adding at least one mineral acid having a concentration in the range of from 2N-6N.

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