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

HRID 1880560Notes

Reaction equation

HRID 1880560 reaction equation
[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]

Participants

8

Reactant 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, compound

Product 1

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

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-aa0fcb6f86dc4fbc920cee7217d7a172
Source dataset
uspto-grants-2012_11
Patent number
US08318748B2

Reaction notes

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