Improved process for the preparation of a dodecapeptide

A process for preparing a peptide of SEQ ID NO:

• 1, comprising the following steps:
• f) grafting of a Fmoc-Gly-MMPA-OH residue to a divinylbenzene-crosslinked polystyrene resin comprising 4-Methylbenzhydrylamine groups,
• g) elongation of the peptide chain with Fmoc protected cys, ser, arg, ser, cys, ser, ser, trp, gly, ser, and trp, in which the protecting group of the side chain of Arg is a 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl, the protecting group of the side chain of Cys is a trityl, the protecting group of the side chain of Ser is a t-butyl, the protecting group of the side chain of Trp is a t-butoxycarbonyl, to obtain a peptide of SEQ ID NO:
• 1 in which the side chains are protected.
• h) simultaneous deprotection of the side chains of the amino-acids and cleavage of the polypeptide from the resin, with a mixture of trifluoroacetic acid, water and 1,4-dithiothreitol, to obtain the polypeptide of SEQ ID NO:
• 1
• i) precipitation of the peptide of SEQ ID NO:
• 1 with a mixture of heptane and MTBE,
• j) purification of the peptide of SEQ ID NO:
• 1 by preparative reverse phase chromatography, characterised in that the peptide of SEQ ID NO:
• 1 is constantly maintained in an aqueous solution comprising an organic solvent,
• k) concentration of the solution containing the peptide of SEQ ID NO:
• 1 obtained in step e), to obtain a concentrated aqueous solution containing the peptide of SEQ ID NO:
• 1 and an organic solvent,
• l) exchange of the trifluoroacetate ion with a pharmaceutically acceptable ion, on a reverse phase chromatographic stationary phase or on an ion exchange resin,
• m) concentration of the aqueous solution containing the peptide of SEQ ID NO:
• 1 obtained in step g), to obtain a concentrated aqueous solution containing the peptide of SEQ ID NO:
• 1 and an organic solvent,
• n) drying of the aqueous solution obtained in step h), to obtain the peptide of SEQ ID NO:
• 1.