Reaction #1869156

ord-ca9f5351d49a4a978457ad82bd1fbd60

Reaction equation

CCCC[C@@H](NC(=O)[C@H](N)CCCNC(=N)N)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCC)C(=O)NCC(=O)N[C@H](Cc1ccc(O)cc1)C(N)=O.O=C(O)C(F)(F)F

TFA (D)Arg-(D)Nle-(D)Nle-(D)Nle-(D)Arg-(D)Nle-(D)Nle-(D)Nle-Gly-(D)Tyr-NH2

phenol

toluene

TFA

→

CC(C)(C)OC(=O)NCC(=O)N[C@H](Cc1ccc(O)cc1)C(N)=O

Boc-Gly-(D)Tyr-NH2

Reactants

—

peptide

TFA (D)Arg-(D)Nle-(D)Nle-(D)Nle-(D)Arg-(D)Nle-(D)Nle-(D)Nle-Gly-(D)Tyr-NH2

phenol

toluene

TFA

Reagents

None

Solvents

THF

Conditions

Detailed conditions

See reaction.notes.procedure_details.

Workup

1
Concentrationconcentrated in vacuo
2
OtherResidual TFA is removed by azeotropic distillation with toluene
3
workup.ADDITIONThe residue is poured into a mixture of petroleum ether and diisopropyl ether
4
FiltrationThe solid is filtered
5
Washwashed with diisopropyl ether
6
Otherdried in vacuo

Procedure

The deprotected peptide SF1257-13 (TFA-(D)Arg-(D)Nle-(D)Nle-(D)Nle-(D)Arg-(D)Nle-(D)Nle-(D)Nle-Gly-(D)Tyr-NH2 (SEQ ID NO:1) is made by slowly adding TFA (A×3 l) to a mixture of SF1257-12 (A kg) and phenol (A×0.1 kg) in toluene and THF while maintaining the temperature at ≦18° C. The reaction mixture is allowed to warm up to room temperature. Following completion of cleavage, the solvent is diluted with THF and then concentrated in vacuo. Residual TFA is removed by azeotropic distillation with toluene. The residue is poured into a mixture of petroleum ether and diisopropyl ether. The solid is filtered, washed with diisopropyl ether and dried in vacuo.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07498309B2uspto-grants-2009_03