L-Leucine → (2S)2-{(S)-[(4-bromophenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid (1-cyanocyclopropyl)-amide

HRID 1880560Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1880560
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:14][C@@H:15]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:16]([OH:18])=O)[C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1.[NH2:23][C:24]1([C:27]#[N:28])[CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C.BrC1C=CC=CC=1[Li].CC(C)CC(N)C12OCC(C)(CO1)CO2.N[C@H](C(O)=O)CC(C)C>>[C:27]([C:24]1([NH:23][C:16](=[O:18])[C@@H:15]([NH:14][C@@H:8]([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=2)[C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[CH2:19][CH:20]([CH3:22])[CH3:21])[CH2:26][CH2:25]1)#[N:28]

Komponenten

8

Edukt 7

HCID 6106L-LeucineHCID 7912DiisopropylamineHCID 5568881-AminocyclopropanecarbonitrileHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574469573-Methyl-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-butylamineHCID 67298316(2S)-2-{(S)-[(4-bromophenyl)thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid2×HCID 178506677HCID 178506677, Verbindung

Produkt 1

HCID 67298346(2S)2-{(S)-[(4-bromophenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid (1-cyanocyclopropyl)-amide

Versuchsvorschrift

The title compound was prepared by the coupling of (2S)-2-{(S)-[(4-bromophenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid with 1-aminocyclopropanecarbonitrile in the presence of HATU and diisopropylamine, in similar manner to that described for the preparation of Example 34. The synthesis of (2S)-2-{(S)-[(4-bromophenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid was accomplished via addition of bromophenyllithium (generated in situ from 1,4-dibromobenzene and n-butyllithium) to the imine condensation product between thiazole 2-carboxyaldehyde and 3-methyl-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-butylamine (L-leucine OBO ester, prepared according to the method described for Example 34), followed by ortho ester deprotection.

Aufarbeitung

  1. customdescribed for the preparation of Example 34
  2. customprepared

Quellen und Nachweise

ORD-Eintrag
ord-aa0fcb6f86dc4fbc920cee7217d7a172
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08318748B2

Notizen zur Reaktion

Wird geladen…