Novel Process For The Preparation Of Leuprolide And Its Pharmaceutically Acceptable Salts Thereof

摘要

The present invention relates to a novel process for the preparation of Leuprolide or its pharmaceutically acceptable salts thereof by solid and solution phase peptide synthesis (Hybrid approach). The present invention also relates to a process for the preparation of Leuprolide or its pharmaceutically acceptable salts thereof by synthesizing the peptide fragments by solid phase (7 and 5 amino acids fragment) and solution phase (2 and 4 amino acids fragment) respectively. The final solution phase condensation of these peptide fragments (7+2 and 5+4) led to a nonapeptide Leuprolide in the protected form. The present invention further relates to novel peptide fragements—Pyr-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-DLeu-Leu-OH (Fragment-11); H-Arg(Pbf)-Pro-NHEt (Fragment-I11); Pyr-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-DLeu-Leu-Arg(Pbf)-Pro-NHEt (Protected Leuprolide) (Fragment-IV); Pyr-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-OH (Fragment-V); H-DLeu-Leu-Arg(Pbf)-Pro-NHEt (Fragment-VI) and process for the preparation thereof.