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

HRID 1009309ノート

反応式

HRID 1009309 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].S1C=CN=C1.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])[CH: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

9

反応物 8

HCID 6106L-LeucineHCID 7912DiisopropylamineHCID 9256ThiazoleHCID 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 865905562-{(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-carboxayldehyde 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-be1d2d3831b346c78bf595a325b75d67
出典データセット
uspto-grants-2011_07
特許番号
US07973037B2

反応ノート

読み込み中…