Method for preparing glucagon-like peptides

A method for preparing a Liraglutide peptide or a salt thereof, comprising:

• (i) providing a solution S comprising a peptide of formula I:
• His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-
• Tyr-Leu-Glu-Gly-Gln-Ala-Ala-B1-Glu Phe-Ile-Ala-
• Trp-Leu-Val-Arg-Gly-Arg-Gly,
• wherein B1 is Lys(palmitoyl-Glu-OH) or Lys(H-Glu-OH);
• (ii) precipitation of the peptide of step (i) by means of mixing solution S with an anti-solvent comprising diisopropyl ether and acetonitrile, wherein the volume ratio (diisopropyl ether:acetonitrile) is in the range of from (3:1) to (10:1);
• and
• (iii) isolating the precipitate obtained from step (ii), preferably by means of filtration and/or centrifugation.

A precursor peptide conjugated to a resin:

• His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-
• Tyr-Leu-Glu-Gly-Gln-Ala-Ala-B2-Glu-Phe-Ile-Ala-
• Trp-Leu-Val-Arg-Gly-Arg-Gly-[resin],
• wherein B2 is Lys (palmitoyl-Glu-OR1) or B2 is Lys (R2-Glu-OR1), with R1 being a carboxylic acid protecting group and R2 being an amino protecting group,
• wherein at least the side chains of Glu, Asp, and Lys bear protecting groups, and wherein at least one pseudoproline dipeptide is present at a position selected from the group consisting of Gly4-Thr5, Phe6-Thr7, Thr7-Ser8, Val10-Ser11, and Ser11-Ser12.