Abstract: The present invention relates to the efficient solid-phase synthesis of liraglutide represented by Formula-I. The present invention relates to an efficient process for the preparation of liraglutide by sequential coupling employing solid phase approach. It involves sequential coupling of protected amino acids to prepare backbone of liraglutide and upon completion of linear sequence, synthesis was extended from lysine side chain by adding ?-glutamic acid and palmitic acid, followed by removal of protective groups, cleavage of the peptide from solid support and purification of crude liraglutide obtained. The present invention also involves the usage of inorganic salts during the coupling, wash with HOBt in DMF solution after Fmoc-deprotection step to suppress the aggregation of peptides and ensure reactions are going for completion, and thus avoid deletion sequences and improve the process yield.

Abstract: The present invention relates to the efficient solid-phase synthesis of liraglutide represented by Formula-I. The present invention relates to an efficient process for the preparation of liraglutide by sequential coupling employing solid phase approach. It involves sequential coupling of protected amino acids to prepare backbone of liraglutide and upon completion of linear sequence, synthesis was extended from lysine side chain by adding ?-glutamic acid and palmitic acid, followed by removal of protective groups, cleavage of the peptide from solid support and purification of crude liraglutide obtained. The present invention also involves the usage of inorganic salts during the coupling, wash with HOBt in DMF solution after Fmoc-deprotection step to suppress the aggregation of peptides and ensure reactions are going for completion, and thus avoid deletion sequences and improve the process yield.