StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Bromide ion → 4'-[[2,3,4,5-Tetrahydro-3(R)-[[3-methyl-1-oxo-3-[[(benzyloxy)carbonyl]amino] butyl]amino]-2-oxo-1H-1-benzazepin-1-yl]methyl]-[1,1'-biphenyl]-2-carboxylic acid 1,1-dimethylethyl ester

HRID 1033415
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1033415
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:30])([CH3:29])[CH2:13][C:14]([NH:16][C@@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[NH:19][C:18]1=[O:28])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[C:42]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[CH:43][CH:44]=[CH:45][CH:46]=2)=[CH:37][CH:36]=1.[Br-]>CN(C)C=O>[CH3:53][C:50]([O:49][C:47]([C:42]1[C:41]([C:38]2[CH:37]=[CH:36][C:35]([CH2:34][N:19]3[C:20]4[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=4[CH2:22][CH2:23][C@@H:17]([NH:16][C:14](=[O:15])[CH2:13][C:12]([CH3:30])([NH:11][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:10])[CH3:29])[C:18]3=[O:28])=[CH:40][CH:39]=2)=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:48])([CH3:51])[CH3:52]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 259Bromide ionHCID 24758Sodium hydrideHCID 9906257tert-Butyl 4'-(bromomethyl)biphenyl-2-carboxylateHCID 105735633-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide

Produkt 1

HCID 22855163
4'-[[2,3,4,5-Tetrahydro-3(R)-[[3-methyl-1-oxo-3-[[(benzyloxy)carbonyl]amino] butyl]amino]-2-oxo-1H-1-benzazepin-1-yl]methyl]-[1,1'-biphenyl]-2-carboxylic acid 1,1-dimethylethyl ester
Ausbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of 1.22 g (3.0 mmol) of 3-benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide (Example 1, Step F) in 10 mL of dry dimethylformamide under nitrogen was added 131.6 mg (3.92 mmol) of 60% sodium hydride in oil. After stirring for 20 minutes, a solution of 1.14 g (3.29 mmol) of t-butyl 4'-bromomethyl-1,1'-biphenyl-2-carboxylate (prepared according to the procedure of D. J. Carini, et. al. EPO publication 324.377) in 2.5 mL of dimethylformamide was added by cannula. The flask which originally contained the bromide was rinsed with 2.5 mL dimethylformamide which was added to the reaction mixture. After stirring at room temperature for 2 hours, the reaction has diluted with 400 mL of ethyl acetate, washed with 100 mL of water and 100 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvent removed under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (55:45) to afford 1.74 g (96%) of the product as a white foam. 1H NMR (200MHz,CDCl3): 1.15 (s,9H), 1.45 (s,3H), 1.48 (s,3H), 1.76 (m,1H), 2.35-2.62 (m,5H), 4.48 (m,1H), 4.79 (d,14Hz,1H), 5.04 (t,12Hz,2H), 5.35 (d, 14Hz,1H), 6.70 (d,6Hz,1H), 7.10-7.45 (m,17H), 7.72 (m,1H). FAB-MS: calculated for C41H45N3O6 675; found 683 (M+Li).

Aufarbeitung

  1. washwas rinsed with 2.5 mL dimethylformamide which
  2. additionwas added to the reaction mixture
  3. stirringAfter stirring at room temperature for 2 hours
  4. additionthe reaction has diluted with 400 mL of ethyl acetate
  5. washwashed with 100 mL of water and 100 mL of brine
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent removed under vacuum
  9. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (55:45)

Quellen und Nachweise

ORD-Eintrag
ord-57ab064fbeb241bf959cc23874f097c8
Quelldatensatz
uspto-grants-1994_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US05310737

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion