Methods of Preparing Sulfinamides and Sulfoxides

Abstract

This invention encompasses novel methods of preparing sulfinamides and sulfoxides, particularly stereomerically pure sulfinamides and sulfoxides. The invention further encompasses novel compounds from which sulfinamides and sulfoxides can be prepared.

1 . A compound of Formula 3:  
     
       
         
         
             
             
         
       
     
     wherein n is 0 to 3; L is CO m R 3  or SO m R 3 , wherein m is 0 to 3; R 1  and R 2  together form a cyclic structure or each of R 1  and R 2  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocycle; R 1′  and R 2′  together form a cyclic structure or each of R 1′  and R 2′  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocycle; R a  and R b  together form a cyclic structure or each of R a  and R b  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocycle; and R 3  is a polymer bound alkyl, aryl or heteroalkyl, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted ester, substituted or unsubstituted ketone, substituted or unsubstituted phosphonate, substituted or unsubstituted phosphonic acid ester, substituted or unsubstituted phosphinoyl, substituted or unsubstituted sulfide, substituted or unsubstituted sulfone, substituted or unsubstituted sulfinyl imine, substituted or unsubstituted heterocycle, or —NR 4 R 5 , wherein R 4  and R 5  together with the nitrogen atom to which they are attached form a heterocycle or each of R 4  and R 5  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, or substituted or unsubstituted heterocycle.  
   
   
       2 . The compound of  claim 1 , which has one of the following structures:  
     
       
         
         
             
             
         
       
     
   
   
       3 . The compound of  claim 1 , which has the structure:  
     
       
         
         
             
             
         
       
     
   
   
       4 . The compound of  claim 3 , which has one of the following stereochemistries:  
     
       
         
         
             
             
         
       
     
   
   
       5 . The compound  claim 1  wherein R 1  is aryl or alkyl.  
   
   
       6 . The compound of  claim 1  wherein R 2  is aryl or alkyl.  
   
   
       7 . The compound of  claim 1  wherein R 3  is substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroalkyl, or aryl.  
   
   
       8 . The compound of  claim 7 , wherein R 3  is halogenated phenyl, 3-methylphenyl, 4-methylphenyl, 1,3,5-trimethylphenyl, 4-(tert-butyl)phenyl, 2-mesityl, tolyl, 2,4,6-triisopropylphenyl, phenyl or biphenyl.  
   
   
       9 . The compound of  claim 7  wherein R 3  is 2-mesityl, tolyl or triisopropylphenyl.  
   
   
       10 . The compound of  claim 1 , which is of the Formula 9:  
     
       
         
         
             
             
         
       
     
     or a salt, solvate, clathrate, or stereomerically pure form thereof.  
   
   
       11 . The compound of  claim 10 , wherein R 3  is halogenated phenyl, 3-methylphenyl, 2-methylphenyl, 2-mesityl, tolyl, 4-(tert-butyl)phenyl, 2,4,6-triisopropylphenyl, phenyl or biphenyl.  
   
   
       12 . The compound of  claim 1 , which is of the Formula 10:  
     
       
         
         
             
             
         
       
     
     or a salt, solvate, clathrate, or stereomerically pure form thereof, wherein each R 10  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, a primary, secondary, or tertiary amine, or a halogen atom; n is an integer of 1 to 4; and m is an integer of 0 to 4.  
   
   
       13 . The compound of  claim 12 , wherein n is 1 and m is 0, 1 or 2.  
   
   
       14 . The compound of  claim 13 , wherein R 3  is halogenated phenyl, 3-methylphenyl, 2-methylphenyl, 2-mesityl, tolyl, 4-(tert-butyl)phenyl, 2,4,6-triisopropylphenyl, phenyl or biphenyl.  
   
   
       15 . The compound of  claim 10  or  claim 12 , wherein said compound is stereomerically pure.  
   
   
       16 . A method of preparing pantoprazole or a derivative, prodrug, salt, solvate, clathrate, or stereomerically pure form thereof, which comprises contacting a compound of  
     
       
         
         
             
             
         
       
       wherein R 1  and R 2  together form a cyclic structure or each of R 1  and R 2  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocycle; R 1′  and R 2′  together form a cyclic structure or each of R 1′  and R 2′  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocycle; and Prot is a protecting group; with a compound of Formula 12:  
       
         
           
           
               
               
           
         
       
       wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of the formula CdZ, BaZ, MgZ, ZnZ, AlZ 2 , MnZ, InZ, or CuZ, and Z is Cl, Br, L aryl, aralkyl, or heterocycle; under conditions suitable for the formation of a compound of Formula 13:  
       
         
           
           
               
               
           
         
       
       and optionally contacting the compound of Formula 13 with a reagent capable of replacing Prot with a hydrogen atom or a cation.  
     
   
   
       17 . The method of  claim 16  wherein the compound of Formula 11 is prepared by contacting a compound of Formula 3 with a compound of Formula 14:  
     
       
         
         
             
             
         
       
     
     wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of the formula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′ 2 , MnZ′, InZ′, or CuZ′, and Z′ is Cl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficient for the formation of the compound of Formula 11.  
   
   
       18 . The method of  claim 16  wherein the compounds of formulas 11 and 13 are enantiomerically pure.  
   
   
       19 . A method of preparing lansoprazole or a derivative, prodrug, salt, solvate, clathrate, or stereomerically pure form thereof, which comprises contacting a compound of Formula 15:  
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 2  together form a cyclic structure or each of R 1  and R 2  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocycle; R 1′  and R 2′  together form a cyclic structure or each of R 1′  and R 2′  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocycle; and Prot is a protecting group; with a compound of Formula 16:  
     
       
         
         
             
             
         
       
     
     wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of the formula CdZ, BaZ, MgZ, ZnZ, AlZ 2 , MnZ, InZ, or CuZ, and Z is Cl, Br, I, aryl, aralkyl, or heterocycle; under conditions suitable for the formation of a compound of Formula 17:  
     
       
         
         
             
             
         
       
     
     and optionally contacting the compound of Formula 17 with a reagent capable of replacing Prot with a hydrogen atom or a cation.  
   
   
       20 . The method of  claim 19  wherein the compound of Formula 15 is prepared by contacting a compound of Formula 3:  
     
       
         
         
             
             
         
       
     
     with a compound of Formula 18:  
     
       
         
         
             
             
         
       
     
     wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of the formula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′ 2 , MnZ′, InZ′, or CuZ′, and Z′ is Cl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficient for the formation of the compound of Formula 15.  
   
   
       21 . The method of  claim 19  wherein the compounds of formulas 15 and 17 are enantiomerically pure.  
   
   
       22 . A method of preparing omeprazole or a derivative, prodrug, salt, solvate, clathrate, or stereomerically pure form thereof, which comprises contacting a compound of Formula 19:  
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 2  together form a cyclic structure or each of R 1  and R 2  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocycle; R 1′  and R 2′  together form a cyclic structure or each of R 1′  and R 2′  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocycle; and Prot is a protecting group; with a compound of Formula 20:  
     
       
         
         
             
             
         
       
     
     wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of the formula CdZ, Baz, MgZ, ZnZ, Ale, MnZ, InZ′, or CuZ, and Z is Cl, Br, I, aryl, aralkyl, or heterocycle; under conditions suitable for the formation of a compound of Formula 21:  
     
       
         
         
             
             
         
       
     
     and optionally contacting the compound of Formula 21 with a reagent capable of replacing Prot with a hydrogen atom or a cation.  
   
   
       23 . The method of  claim 22  wherein the compound of Formula 19 is prepared by contacting a compound of Formula 3:  
     
       
         
         
             
             
         
       
     
     with a compound of Formula 22:  
     
       
         
         
             
             
         
       
     
     wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of the formula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′ 2 , MnZ′, InZ′, or CuZ′, and Z′ is Cl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficient for the formation of the compound of Formula 19.  
   
   
       24 . The method of  claim 22  wherein the compounds of formulas 19 and 21 are enantiomerically pure.  
   
   
       25 . A method of preparing rabeprazole or a derivative, prodrug, salt, solvate, clathrate, or stereomerically pure form thereof, which comprises contacting a compound of Formula 15:  
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 2  together form a cyclic structure or each of R 1  and R 2  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocycle; R 1′  and R 2′  together form a cyclic structure or each of R 1′  and R 2′  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocycle; and Prot is a protecting group; with a compound of Formula 23:  
     
       
         
         
             
             
         
       
     
     wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of the formula CdZ, BaZ, MgZ, ZnZ, AlZ, MnZ, InZ, or CuZ, and Z is Cl, Br, L aryl, aralkyl, or heterocycle; under conditions suitable for the formation of a compound of Formula 24:  
     
       
         
         
             
             
         
       
     
     and optionally contacting the compound of Formula 24 with a reagent capable of replacing Prot with a hydrogen atom or a cation.  
   
   
       26 . The method of  claim 25  wherein the compound of Formula 15 is prepared by contacting a compound of Formula 3:  
     
       
         
         
             
             
         
       
     
     with a compound of Formula 18:  
     
       
         
         
             
             
         
       
     
     wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, lni Cu, or is of the formula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′ 2 , MnZ′, InZ′, or CuZ′, and Z′ is Cl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficient for the formation of the compound of Formula 23.  
   
   
       27 . The method of  claim 25  wherein the compounds of formulas 23 and 24 are enantiomerically pure.  
   
   
       28 . A compound of Formula 7:  
     
       
         
         
             
             
         
       
     
     or a salt, solvate, clathrate, or stereomerically pure form thereof, wherein R 3  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, substituted or unsubstituted heterocycle, or —NR 4 R 5 , wherein R 4  and R 5  together with the nitrogen atom to which they are attached form a heterocycle or each of R 4  and R 5  is independently hydrogen, is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, or substituted or unsubstituted heterocycle; each R 10  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, a primary, secondary, or tertiary amine, a heterocycle, or a halogen atom; n is an integer of 1 to 4; and m is an integer of 0 to 4.  
   
   
       29 . A compound of Formula 25:  
     
       
         
         
             
             
         
       
     
     or a salt, solvate, clathrate, or stereomerically pure form thereof, wherein R 1  and R 2  together form a cyclic structure or each of R 1  and R 2  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocycle; R 3  is substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, substituted or unsubstituted heterocycle, or —NR 4 R 5 , wherein R 4  and R 5  together with the nitrogen atom to which they are attached form a heterocycle or each of R 4  and R 5  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, or substituted or unsubstituted heterocycle; each R 11  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, a primary, secondary, or tertiary amine, a heterocycle, or a halogen atom; R 12  is substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, or substituted or unsubstituted heterocycle, or is a sulfoxide; and r is an integer from 0 to 4.  
   
   
       30 . The compound of  claim 29  wherein said compound is of Formula 26:  
     
       
         
         
             
             
         
       
     
     or a salt, solvate, clathrate, or stereomerically pure form thereof, wherein each R 11  is independently substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, a primary, secondary, or tertiary amine, a heterocycle, or a halogen atom; R 12  is substituted or unsubstituted alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted ether, substituted or unsubstituted sulfide, or substituted or unsubstituted heterocycle, or is a sulfoxide; and r is an integer from 0 to 4.