Novel pharmaceutical intermediates and methods for preparing the same

Abstract

A pharmaceutical intermediate including a first indole moiety which is associated with an optionally carboxylated hexahydroazepino moiety, an optionally carboxylated azonane moiety, or a second, optionally carboxylated indole moiety, having an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl substituent pendant from a nitrogen atom of the same.

What is claimed and desired to be secured by Letters Patent of the United States is: 
     
         1 . A pharmaceutical intermediate comprising the structure of formula I: 
       
         
           
           
               
               
           
         
         wherein:
 R 1 -R 4 , R 6 -R 8 , and R 10 -R 14  are each independently selected from the group consisting of H; OH; and an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); 
 R 5  is selected from the group consisting of an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); 
 R 9  is selected from the group consisting of H; OH; and an alcohol, ether, ester, amide, hydrazide, cyanide, and/or ketone group containing approximately 1 to approximately 25 carbon atom(s); and 
 
         X 1 -X 2  are each independently selected from the group consisting of N, O, and S. 
       
     
     
         2 . The pharmaceutical intermediate according to  claim 1 , comprising the structure of formula II: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is selected from the group consisting of an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); 
 R 2  is selected from the group consisting of H; OH; and an alcohol, ether, ester, amide, hydrazide, cyanide, and/or ketone group containing approximately 1 to approximately 25 carbon atom(s); and 
 R 3  is selected from the group consisting of H; OH; and an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s). 
 
       
     
     
         3 . The pharmaceutical intermediate according to  claim 1 , comprising the structure of formula III: 
       
         
           
           
               
               
           
         
         wherein:
 wherein R 1  is selected from the group consisting of an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s). 
 
       
     
     
         4 . The pharmaceutical intermediate according to  claim 1 , comprising the structure of formula IV: 
       
         
           
           
               
               
           
         
         wherein:
 R 1 -R 3  are each independently selected from the group consisting of H, CH 3 , and C 6 H 5 . 
 
       
     
     
         5 . The pharmaceutical intermediate according to  claim 1 , comprising methyl 3-allyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate. 
     
     
         6 . The pharmaceutical intermediate according to  claim 1 , comprising methyl 3 cinnamyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate. 
     
     
         7 . The pharmaceutical intermediate according to  claim 1 , comprising methyl 3-(2-phenylallyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate. 
     
     
         8 . The pharmaceutical intermediate according to  claim 1 , comprising methyl 3-(3-methylbut-2-en-1-yl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate. 
     
     
         9 . A pharmaceutical intermediate comprising the structure of formula V: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is selected from the group consisting of an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); 
 R 2 -R 4  and R 6  are each independently selected from the group consisting of H; OH; and an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); and 
 R 5  is selected from the group consisting of H; OH; and an alcohol, ether, ester, amide, hydrazide, cyanide, and/or ketone group containing approximately 1 to approximately 25 carbon atom(s). 
 
       
     
     
         10 . The pharmaceutical intermediate according to  claim 9 , comprising the structure of formula VI: 
       
         
           
           
               
               
           
         
         wherein:
 R 1 -R 3  are each independently selected from the group consisting of H, CH 3 , and C 6 H 5 ; 
 R 4  is selected from the group consisting of an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); and 
 n is an integer ranging from approximately 2 to approximately 5. 
 
       
     
     
         11 . The pharmaceutical intermediate according to  claim 9 , comprising the structure of formula VII: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The pharmaceutical intermediate according to  claim 9 , comprising the structure of formula VIII: 
       
         
           
           
               
               
           
         
       
     
     
         13 . A pharmaceutical intermediate comprising the structure of formula IX: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is selected from the group consisting of an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); 
 R 2 -R 4  and R 6  are each independently selected from the group consisting of H; OH; and an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); and 
 R 5  is selected from the group consisting of H; OH; and an alcohol, ether, ester, amide, hydrazide, cyanide, and/or ketone group containing approximately 1 to approximately 25 carbon atom(s). 
 
       
     
     
         14 . The pharmaceutical intermediate according to  claim 13 , comprising the structure of formula X: 
       
         
           
           
               
               
           
         
         wherein:
 R 1 -R 3  are each independently selected from the group consisting of H, CH 3 , and O 6 H 5 ; 
 
         R 4  is selected from the group consisting of an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); and
 n is an integer ranging from approximately 2 to approximately 5. 
 
       
     
     
         15 . The pharmaceutical intermediate according to  claim 13 , comprising the structure of formula XI: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The pharmaceutical intermediate according to  claim 13 , comprising the structure of formula XII: 
       
         
           
           
               
               
           
         
       
     
     
         17 . A pharmaceutical intermediate comprising at least one of the structures of formulae II, V, IX, and combinations thereof: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is selected from the group consisting of an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); 
 R 2  of formulae (V) and (IX), R 3 , R 4 , and R 6  are each independently selected from the group consisting of H; OH; and an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, and/or alkyl-alkenyl group containing approximately 1 to approximately 25 carbon atom(s); and 
 R 2  of formula (II), and R 5  are each independently selected from the group consisting of H; OH; and an alcohol, ether, ester, amide, hydrazide, cyanide, and/or ketone group containing approximately 1 to approximately 25 carbon atom(s). 
 
       
     
     
         18 . A pharmaceutical intermediate, comprising: a first indole moiety which is associated with an optionally carboxylated hexahydroazepino moiety, an optionally carboxylated azonane moiety, or a second, optionally carboxylated indole moiety, having at least one of an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and alkyl-alkenyl substituent pendant from a nitrogen atom of the same.