Patent ID: 7507791
Filing Date: 2009-03-24
Classification: C07K

Abstract:
1. 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, wherein the solid phase support is a 2-chlorotritylchloride-polystyrene resin and wherein further the first coupling agent/additive system is selected from the group consisting of DCC/HOBt, HBTU/HOBt, TBTU/HOBt, HATU/HOAt DEPBT/HOOBt, and PyBoP/Cl-HOBt, 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 wherein R has the meaning of p-aminophenyl and wherein one amino group is protected with an amino protecting group, wherein the second coupling agent/additive system for the reaction of the peptide intermediate of formula II with the aniline of formula III is selected from the group consisting of DCC/HOBt, HATU/HOAt, HBTU/HOBt, TBTU/HOBt, PyBOP/Cl-HOBt and DEPBT/HOOBt.