Novel piperidino-dihydrothienopyrimidine sulfoxides and their use for treating copd and asthma

Abstract

Piperidino-dihydrothienopyrimidine sulfoxides of formula I wherein: Ring A is a 6-membered aromatic ring optionally comprising one or two nitrogen atoms and R is Cl and is located in the para-, meta-, or ortho-position of Ring A, S* is a sulphur atom that represents a chiral center, and all pharmaceutically acceptable salts, enantiomers and racemates, hydrates and solvates thereof and the use of these compounds for the treatment of inflammatory or allergic diseases of the respiratory tract such as COPD or asthma.

1 . A method of manufacturing the compound A 
       
         
           
           
               
               
           
         
         wherein HX is a pharmaceutically acceptable acid, 
         comprising the steps a) and b), wherein in 
         step a) compound B 
       
       
         
           
           
               
               
           
         
         
           wherein HY is a pharmaceutically acceptable acid, 
           is reduced by borane and wherein in 
           step b) a pharmaceutically acceptable acid HX is added in order to obtain compound A. 
         
       
     
     
         2 . The method of  claim 1 , wherein the borane for the reduction in step a) is added directly. 
     
     
         3 . The method of  claim 1 , wherein the borane for the reduction in step a) is generated in-situ. 
     
     
         4 . The method of  claim 3 , wherein the borane for the reduction in step a) is generated either from the combination of NaBH 4  and I 2  or from the combination of NaBH 4  and BF 3 —OEt 2 . 
     
     
         5 . The method of  claim 1 , wherein HX is either tosylic acid or hydrochloric acid. 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutically acceptable acid HY in compound B is HCl.