N-formyl derivatives of paroxetine

Abstract

A compound or composition comprising N-formyl paroxetine of formula (1) is useful as a pharmaceutical and as a synthetic intermediate. The N-formyl paroxetine can be an impurity in paroxetine substances and methods of assaying for such an impurity are also useful.

We claim:  
     
         1 . A process which comprises treating an N-formyl paroxetine compound of formula (1)  
       
         
           
           
               
               
           
         
       
       with a de-formylation agent.  
     
     
         2 . The process according to  claim 1 , wherein said de-formylation agent is an organic or inorganic acid.  
     
     
         3 . The process according to  claim 2 , wherein said acid is selected from the group consisting of hydrochloric acid, acetic acid, formic acid, methane sulfonic acid, maleic acid, and tartaric acid.  
     
     
         4 . The process according to  claim 2 , wherein said de-formylation agent is a pharmaceutically acceptable acid and said treating step forms a corresponding pharmaceutically acceptable salt of paroxetine.  
     
     
         5 . The process according to  claim 4 , wherein said treating step occurs in a solvent.  
     
     
         6 . The process according to  claim 5 , wherein said acid is methane sulfonic acid and said treating step forms paroxetine methane sulfonate.  
     
     
         7 . The process according to  claim 5 , wherein said acid is hydrochloric acid and said treating step forms dissolved and/or solid paroxetine hydrochloride.  
     
     
         8 . A process, which comprises: 
 ingesting into a human or animal body a pharmaceutical composition comprising paroxetine hydrochloride and an N-formyl paroxetine compound of formula (1)                          and    contacting in vivo said N-formyl paroxetine compound with hydrochloric acid to form a paroxetine hydrochloride.    
     
     
         9 . The process according to  claim 8 , wherein said pharmaceutical composition contains 0.1 to 99.97% paroxetine hydrochloride based on the total amount of paroxetine hydrochloride and N-formyl paroxetine compound.  
     
     
         10 . The process according to  claim 9 , wherein said pharmaceutical composition contains 0.1 to 99.95% paroxetine hydrochloride based on the total amount of paroxetine hydrochloride and N-formyl paroxetine compound.  
     
     
         11 . The process according to  claim 10 , wherein said pharmaceutical composition contains 0.1 to 99.9% paroxetine hydrochloride based on the total amount of paroxetine hydrochloride and N-formyl paroxetine compound.  
     
     
         12 . The process according to  claim 8 , wherein said paroxetine hydrochloride in said pharmaceutical composition is a crystalline paroxetine hydrochloride anhydrate.  
     
     
         13 . The process according to  claim 9 , wherein said paroxetine hydrochloride in said pharmaceutical composition is a crystalline paroxetine hydrochloride anhydrate.  
     
     
         14 . The process according to  claim 10 , wherein said paroxetine hydrochloride in said pharmaceutical composition is a crystalline paroxetine hydrochloride anhydrate.  
     
     
         15 . The process according to  claim 8 , wherein said pharmaceutical composition is a tablet and further comprises a calcium phosphate, a cellulose, a starch and/or lactose.  
     
     
         16 . The process according to  claim 10 , wherein said pharmaceutical composition is a tablet and further comprises a calcium phosphate, a cellulose, a starch and/or lactose.  
     
     
         17 . The process according to  claim 8 , wherein said paroxetine hydrochloride resulting from said contacting step is dissolved paroxetine hydrochloride.  
     
     
         18 . A pharmaceutical tablet comprising 1-50 mg of a crystalline paroxetine hydrochloride anhydrate, at least one pharmaceutically acceptable excipient, and an N-formyl paroxetine compound of formula (1)  
       
         
           
           
               
               
           
         
       
     
     
         19 . The tablet according to  claim 18 , wherein the amount of N-formyl paroxetine compound is at least 0.03% based on the combined weight of the N-formyl paroxetine compound and the paroxetine hydrochloride.  
     
     
         20 . The tablet according to  claim 19 , wherein the amount of N-formyl paroxetine compound is at least 0.05% based on the combined weight of the N-formyl paroxetine compound and the paroxetine hydrochloride.  
     
     
         21 . The tablet according to  claim 20 , wherein the amount of N-formyl paroxetine compound is at least 0.1% based on the combined weight of the N-formyl paroxetine compound and the paroxetine hydrochloride.  
     
     
         22 . The tablet according to  claim 18 , wherein said at least one excipient comprises at least a calcium phosphate, a cellulose, a starch and/or lactose.  
     
     
         23 . The tablet according to  claim 19 , wherein said at least one excipient comprises at least a calcium phosphate, a cellulose, a starch and/or lactose.  
     
     
         24 . The tablet according to  claim 20 , wherein said at least one excipient comprises at least a calcium phosphate, a cellulose, a starch and/or lactose.  
     
     
         25 . The tablet according to  claim 19 , wherein said N-formyl paroxetine compound is the trans 3S, 4R enantiomer.