Process for preparation of palbociclib

Abstract

The present application relates to a process for the preparation of crystalline form A of palbociclib having specific surface area more than 2 m 2 /g comprising one-pot process for the preparation of compound of formula (IV). The present application further relates to the preparation of acid-addition salts of palbociclib and their use for the synthesis of crystalline form A of palbociclib having specific surface area more than 2 m 2 /g.

1 - 6 . (canceled) 
     
     
         7 . A process for preparation of Palbociclib comprising a one pot process for preparation of a compound of formula (IV) comprising the steps of:
 (a) reacting a compound of formula (I) with a compound of formula (II) to provide a compound of formula (III)   
       
         
           
           
               
               
           
         
         (b) reacting the compound of formula (III) with n-butyl vinyl ether to provide compound of formula (IV) 
       
       
         
           
           
               
               
           
         
         (c) treating compound of formula (IV) with an acid to provide an acid-addition salt of palbociclib; 
         (d) treating acid-addition salt of palbociclib with a base. 
       
     
     
         8 . The process of  claim 7 , wherein the acid used in step (a) is selected from a group oxalic acid, trifluoro acetic acid, methane sulfonic acid and isethionic acid. 
     
     
         9 . The process of  claim 7 , wherein the base is sodium hydroxide. 
     
     
         10 . Crystalline form A of palbociclib having specific surface area more than 2 m 2 /g, as prepared by the process of  claim 7 . 
     
     
         11 . The process of  claim 7 , wherein step (a) is carried out in presence of a Grignard reagent. 
     
     
         12 . The process of  claim 7 , wherein step (b) is carried out in presence of a palladium catalyst and a base. 
     
     
         13 . The process of  claim 12 , wherein the palladium catalyst is PdCl 2 (dppf). 
     
     
         14 . The process of  claim 12 , wherein the base is diisopropyl ethylamine. 
     
     
         15 . The process of  claim 7 , wherein compound of formula (IV) is treated with an aqueous solution of L-cysteine