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

HRID 1880560ノート

反応式

HRID 1880560 の反応式
[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]

参加物

8

反応物 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 回HCID 178506677HCID 178506677、化合物

生成物 1

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

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-aa0fcb6f86dc4fbc920cee7217d7a172
出典データセット
uspto-grants-2012_11
特許番号
US08318748B2

反応ノート

読み込み中…