Solid phase peptide synthesis of tri-peptide derivatives

A process for the preparation of a peptide derivative or a pharmaceutically acceptable salt thereof of formula I

• wherein tos has the meaning of p-toluenesulfonyl,
• comprising
• a) consecutive coupling of the amino acids arginine, proline and glycine on a solid phase support in the presence of a first coupling agent/additive system:
• b) tosylation of the N-α-amino group of the glycine moiety,
• c) cleavage of the tosylated peptide or of an amino side chain protected derivative thereof from the solid phase support to form the peptide intermediate of formula II
• or an amino side chain protective derivative thereof;
• and
• d) reaction, in the presence of a second coupling agent/additive system, of the peptide intermediate of the formula
• or of an amino side chain protected derivative thereof
• with an aniline of the formula
• R—NH2 III
• wherein R has the meaning of p-aminophenyl and wherein one amino group is protected with an amino protecting group.