Synthesis of 11-aryl-5,6,-dihydro-11H-dibenz [b,e] azepines

Abstract

Disclosed is a three step synthesis of 11-aryl-5,6-dihydro-11H-dibenz[b,e]azepines from a 2-aminobenzophenone represented by the following structural formula: and a starting material represented by the following structural formula: ,2 Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or substituted with one, two or three substituents. Each substituent on Phenyl Ring A, Phenyl Ring B and Phenyl Ring C is independently chosen. R is —H, a aliphatic group, a substituted aliphatic group, an aryl group, a substituted aryl group, —C(O)—R′, —C(O)—H, —C(O)—NHR′, —S(O) 2 R′, —C(O)—C(O)—R′, —C(O)—C(O)—H, —C(S)—R′, —C(S)—H, —C(O)—OR′, —C(S)—OR′, —C(O)—SR′, —C(S)—SR′, —C(O)—NR′ 2 or —C(O)—C(S)—R′. R′ is an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 1 is a leaving group. The present invention also includes novel compounds which are intermediates in the preparation of 11-aryl-5,6-dihydro-11H-dibenz[b,e]azepines.

What is claimed is:  
     
         1 . A method of preparing a diphenyl ketone represented by the following structural formula:  
                   
       wherein: 
 Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or substituted with one, two or three substituents, wherein each substituent is independently chosen; and  
 R is —H, an aliphatic group, a substituted aliphatic group, an aryl group, a substituted aryl group, —C(O)—R′, —C(O)—H, —C(O)—NHR′, —S(O) 2 R′, —C(O)— C(O)—R′, —C(O)—C(O)—H, —C(S)—R′, —C(S)—H, —C(O)—OR′, —C(S)—OR′, —C(O)—SR′, —C(S)—SR′, —C(O)—NR′ 2  or —C(O)— C(S)—R′, wherein R′ is an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;  
 said method comprising reacting a base, a 2-aminobenzophenone represented by the following structural formula:  
                 
 
  and a starting material represented by the following structural formula:  
                 
 
  wherein R 1  is a leaving group.  
 
     
     
         2 . The method of    claim 1    wherein Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or monosubstituted.  
     
     
         3 . The method of    claim 2    wherein R 1  is a halide.  
     
     
         4 . The method of    claim 3    wherein the 2-aminobenzophenone is represented by the following structural formula:  
                 
 
       the starting material is represented by the following structural formula:  
                 
 
       wherein: 
 R is —H, —CH 3 , benzyl, —C(O)—OCH 3 , —C(O)—C(O)—OH, —C(O)—C(O)—OCH 2 CH 3 , para-chlorobenzoyl, —C(O)—O-(phenyl), benzoyl, meta-methoxybenzoyl, para-nitrobenzoyl, para-methoxybenzoyl, para-methylbenzoyl, para-chlorobenzoyl, naphthoyl, —C(O)—NH-(phenyl), para-methylaminobenzoyl, para-aminobenzoyl or —C(O)—NH-(4-NO 2 -phenyl);  
 R 2  is —H, —F, —Cl, —Br or —I;  
 R 3  and R 5  are independently —H, —OCH 3 , —OCH 2 CH 3 , —F, —Cl, —Br or —I;  
 R 4  is —H or, taken together with R 3  and the carbon atoms to which R 3  and R 4  are bonded, a phenyl group; and  
 R 6  is —H, —F, —Cl, —Br or —I.  
 
     
     
         5 . The method of    claim 4    wherein R 1  is a halide.  
     
     
         6 . The method of    claim 4    wherein: 
 a) the base is potassium carbonate;  
 b) the halide is —Cl or —Br; and  
 c) the diphenyl ketone is prepared by reacting sodium iodide, the base, the substituted 2-aminobenzophenone and the starting material.  
 
     
     
         7 . A method of preparing a compound represented by the following structural formula:  
                   
       wherein: 
 Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or substituted with one, two or three substituents, wherein each substituent is independently chosen; and  
 R is —H, an aliphatic group, a substituted aliphatic group, an aryl group, a substituted aryl group, —C(O)—R′, —C(O)−H, —C(O)—NHR′, —S(O) 2 R′, —C(O)— C(O)—R′, —C(O)—C(O)—H, —C(S)—R′, —C(S)—H, —C(O)—OR′, —C(S)—OR′, —C(O)—SR′, —C(S)—SR′, —C(O)—NR′ 2  or —C(O)—C(S)—R′, wherein R′ is an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;  
 comprising reacting a ketone reducing agent with a diphenyl ketone represented by the following structural formula:  
                 
 
 
     
     
         8 . The method of    claim 7    wherein Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or monosubstituted.  
     
     
         9 . The method of    claim 8    wherein the ketone reducing agent is a hydride reducing agent.  
     
     
         10 . The method of    claim 9    wherein the hydride reducing agent is sodium borohydride.  
     
     
         11 . The method of    claim 10    wherein the diphenyl ketone is represented by the following structural formula:  
                 
 
       wherein: 
 R is —H, —CH 3 , benzyl, —C(O)—OCH 3 , —C(O)—C(O)—OH, —C(O)—C(O)—OCH 2 CH 3 , para-chlorobenzoyl, —C(O)—O-(phenyl), benzoyl, meta-methoxybenzoyl, para-nitrobenzoyl, para-methoxybenzoyl, para-methylbenzoyl, para-chlorobenzoyl, naphthoyl, —C(O)—NH-(phenyl), para-methylaminobenzoyl, para-aminobenzoyl or —C(O)— NH-(4-NO 2 -phenyl);  
 R 2  is —H, —F, —Cl, —Br or —I;  
 R 3  and R 5  are independently —H, —OCH 3 , —OCH 2 CH 3 , —F, —Cl, —Br or —I;  
 R 4  is —H or, taken together with R 3  and the carbon atoms to which R 3  and R 4  are bonded, a phenyl group; and  
 R 6  is —H, —F, —Cl, —Br or —I.  
 
     
     
         12 . The method of    claim 7    wherein the diphenyl ketone is prepared by reacting a base, a substituted 2-aminobenzophenone represented by the following structural formula:  
                 
 
       and a starting material represented by the following structural formula:  
                 
 
       wherein R 1  is a leaving group.  
     
     
         13 . The method of    claim 12    wherein Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or monosubstituted.  
     
     
         14 . The method of    claim 13    wherein R 1  is a halide.  
     
     
         15 . The method of    claim 14    wherein: 
 a) the base is potassium carbonate;  
 b) the halide is —Cl or —Br; and  
 c) the diphenyl ketone is prepared by reacting sodium iodide, the base, the substituted 2-aminobenzophenone and the starting material.  
 
     
     
         16 . A compound represented by the following structural formula:  
                   
       and salts thereof;  
       wherein: 
 Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or substituted with one, two or three substituents, wherein each substituent is independently chosen;  
 R is —H, an aliphatic group, a substituted aliphatic group, an aryl group, a substituted aryl group; —C(O)—R′, —C(O)—H, —C(O)—NHR′, —S(O) 2 R′, —C(O)— C(O)—R′, —C(O)—C(O)—H, —C(S)—R′, —C(S)—H, —C(O)—OR′, —C(S)—OR′, —C(O)—SR′, —C(S)—SR′, —C(O)—NR′ 2  or —C(O)— C(S)—R′, wherein R′ is an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group.  
 
     
     
         17 . The compound of    claim 16    wherein Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or monosubstituted.  
     
     
         18 . The compound of    claim 17    wherein the compound is represented by the following structural formula:  
                 
 
       wherein: 
 R is —H, —CH 3 , benzyl, —C(O)—OCH 3 , —C(O)—C(O)—OH, —C(O)—C(O)—OCH 2 CH 3 , para-chlorobenzoyl, —C(O)—O-(phenyl), benzoyl, meta-methoxybenzoyl, para-nitrobenzoyl, para-methoxybenzoyl, para-methylbenzoyl, para-chlorobenzoyl, naphthoyl, —C(O)—NH-(phenyl), para-methylaminobenzoyl, para-aminobenzoyl or —C(O)— NH-(4-NO 2 -phenyl);  
 R 2  is —H, —F, —Cl, —Br or —I;  
 R 3  and R 5  are independently —H, —OCH 3 , —OCH 2 CH 3 , —F, —Cl, —Br or —I;  
 R 4  is —H or, taken together with R 3  and the carbon atoms to which R 3  and R 4  are bonded, a phenyl group; and  
 R 6  is —H, —F, —Cl, —Br or —I.  
 
     
     
         19 . A compound represented by the following structural formula:  
                   
       and salts thereof;  
       wherein: 
 Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or substituted with one, two or three substituents, wherein each substituent is independently chosen with the provisos that 1) at least one of Ring A, Ring B or Ring C is substituted;  2) when Ring B and Ring C are unsubstituted, Ring A is not substituted with —Cl para to the carbon bonded to the nitrogen atom; and  3; when Ring A and Ring C are unsubstituted, Ring B is not substituted with —OCH 3  at positions three, four and five relative to the carbon atom bonded to the methyl amino group; and  
 R is —H, an aliphatic group, a substituted aliphatic group, an aryl group, a substituted aryl group; —C(O)—R′, —C(O)—H, —C(O)—NHR′, —S(O) 2 R′, —C(O)—C(O)—R′, —C(O)—C(O)—H, —C(S)—R′, —C(S)—H, —C(O)—OR′, —C(S)—OR′, —C(O)—SR′, —C(S)—SR′, —C(O)—NR′ 2  or —C(O)—C(S)—R′, wherein R′ is an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group.  
 
     
     
         20 . The compound of    claim 19    wherein Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or monosubstituted.  
     
     
         21 . The compound of    claim 20    wherein the compound is represented by the following structural formula:  
                 
 
       wherein: 
 R is —H, —CH 3 , benzyl, —C(O)—OCH 3 , —C(O)—C(O)−OH, —C(O)−C(O)—OCH 2 CH 3 , para-chlorobenzoyl, —C(O)—O-(phenyl), benzoyl, meta-methoxybenzoyl, para-nitrobenzoyl, para-methoxybenzoyl, para-methylbenzoyl, para-chlorobenzoyl, naphthoyl, —C(O)—NH-(phenyl), para-methylaminobenzoyl, para-aminobenzoyl or —C(O)—NH-(4-NO 2 -phenyl) ;  
 R 2  is —H, —F, —Cl, —Br or —I;  
 R 3  and R 5  are independently —H, —OCH 3 , —OCH 2 CH 3 , —F, —Cl, —Br or —I;  
 R 4  is —H or, taken together with R 3  and the carbon atoms to which R 3  and R 4  are bonded, a phenyl group; and  
 R 6  is —H, —F, —Cl, —Br or —I.