Preparation of somatostatin peptides

1. A process for producing a compound of formula I

wherein

R 1 is —C 2-6 alkylene-NR 3 R 4 , —C 2-6 alkylene-guanidine or —C 2-6 alkylene-COOH wherein each of R 3 and R 4 independently is H, C 1-4 alkyl, ω-hydroxy-C 2-4 alkylene oracyl or R 3 and R 4 form together with the nitrogen atom to which they are attached a heterocyclic group which may comprise a further heteroatom, and

R 2 is Z 1 -CH 2 —R 5 , —CH 2 —CO—O—CH 2 —R 5 ,

 wherein Z 1 is O or S and R 5 is optionally substituted phenyl,

or a salt thereof,

comprising cyclizing a linear somatostatin analogue of formula II

with a cyclizing agent selected from O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexaflurophosphate and 1-hydroxybenzotriazole,

wherein R 1 and R 2 are as defined above,

each of R 11 and R 12 , independently, is an amino protecting group

whereby when R 1 comprises a terminal NH 2 , this terminal NH 2 is also protected by an amino protecting group,

and where required removing the protecting group(s),

and recovering a compound of formula I thus obtained in free form or in salt form.

2. A process according to claim 1 comprising cyclizing a linear somatostatin analogue of formula II

wherein R 1 is —CH 2 —CH 2 —NR 3 R 4 , R 2 is 4-benzyloxy-phenyl, and R 3 , R 4 , R 11 and R 12 are as defined in claim 1 ,

whereby when R 1 comprises a terminal NH 2 , this terminal NH 2 is also protected by an amino protecting group,

and where required removing the protecting group(s),

and recovering a compound of formula I thus obtained in free form or in salt form wherein R 1 is —CH 2 —CH 2 —NR 3 R 4 and R 2 is 4-benzyloxy-phenyl.

3. A compound of formula II according to claim 2 which is selected from

H-Tyr(Bzl)-Phe-(2S,4R)-4-(Boc-NH—CH 2 —CH 2 —NH—CO—O)-Pro-DPhg-DTrp(Boc)-Lys(Boc)-OH,

H-Tyr(Bzl)-Phe-(2S,4R)-4-(Boc-NH—CH 2 —CH 2 —NH—CO—O)-Pro-Phg-DTrp-Lys(Boc)-OH and

H-Tyr(Bzl)-Phe-(2S,4R)-4-(Boc-NH—CH 2 —CH 2 —NH—CO—O)-Pro-Phg-D-Trp(Boc)Lys(Boc)-OH or a salt thereof.