A PROCESS FOR THE PREPARATION OF CINACALCET AND ITS SALTS

摘要

A process for preparing (cinacalcet) a-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-l- naphthalenemethanamine (formula I): or a pharmaceutically acceptable salt thereof which comprises: a) reacting 1-acetonaphthone with an alkyl amine or a substituted or non-substituted aralkyl amine in presence of a suitable solvent to form imine compound (formula III), which on reduction using suitable reducing agent yields N-substituted naphthyl ethyl amine (formula IV). b) Optionally resolving the N-substituted naphthyl ethyl amine (formula (IV) into its corresponding (R) or (S) isomer (formula IVa and IVb). c) Further reacting the (R,S) or (R) or (S)-N-substituted naphthyl ethyl amine (formula IV, IVa, or IVb) with trifluoromethyl aryl alkyl compound (formula V) in presence of a base and in a suitable solvent to form an intermediate corresponding to (R5S), (R) or (S)-N-substituted- methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-l-naphthalenemethanamine (N-substituted- cinacalcet) (formula VI, Via or VIb). d) Optionally resolving (R,S)-N-substituted cinacalcet (formula VI) into its corresponding (R) and (S) isomers (formula Via or VIb). e) Converting (R5S) or (R) or (S)-N-substituted-cinacalcet (formula VI, Via or VIb) to the corresponding (R5S) or (R) or (S)-a-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-l- naphthalenemethanamine (cinacalcet) (formula, I5 Ia or Ib)) by dealkylation or debenzylation, f) Optionally resolving (R,S)-a-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-l- naphthalenemethanamine (cincacalcet, formula I) into (R) and (S)-a-methyl-N-[3-[3- (trifluoromethyl)phenyl]propyl]-l-naphthalenemethanamine (formula Ia and Ib) using a suitable resolving agent.