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4-(Methylthio)phenylboronic acid → N1-(cyanomethyl)-N2-{[4-(methylsulfonyl)phenyl][4'-(methylthio)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

HRID 1009241
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1009241
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=2)[NH:9][C@H:10]([C:15]([NH:17][CH2:18][C:19]#[N:20])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:4][CH:3]=1.[CH3:31][S:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:19]([CH2:18][NH:17][C:15](=[O:16])[C@H:10]([CH2:11][CH:12]([CH3:14])[CH3:13])[NH:9][CH:8]([C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1)[C:5]1[CH:6]=[CH:7][C:2]([C:36]2[CH:37]=[CH:38][C:33]([S:32][CH3:31])=[CH:34][CH:35]=2)=[CH:3][CH:4]=1)#[N:20]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 2

HCID 27339594-(Methylthio)phenylboronic acidHCID 44403034N2-{(4-bromophenyl)[4-(methylsulfonyl)phenyl]methyl}-N1-(cyanomethyl)-L-leucinamide

Produkt 1

HCID 86609682N1-(cyanomethyl)-N2-{[4-(methylsulfonyl)phenyl][4'-(methylthio)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Katalysator
HCID 80711,2-DimethoxyethaneLösungsmittel
HCID 10340Sodium CarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A heterogeneous mixture of N2-{(4-bromophenyl)[4-(methylsulfonyl)phenyl]methyl}-N1-(cyanomethyl)-L-leucinamide from step 4 (72 mg, 0.15 mmol), 4-(methylthio)phenylboronic acid (37 mg, 0.22 mmol) in ethylene glycol dimethyl ether (11 mL) and 2M aqueous sodium carbonate was degassed under vacuum and purged with nitrogen. To this mixture was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (19 mg, 0.023 mmol), followed by degassing and purging with nitrogen. The reaction mixture was heated at 85° C. for 16 hours with efficient stirring. The reaction mixture was partitioned between EtOAc and aqueous NH4OAc 25% w/v. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by chromatography using EtOAc and hexane as eluant to give the title compound as a colorless gum.

Aufarbeitung

  1. customwas degassed under vacuum
  2. custompurged with nitrogen
  3. customby degassing
  4. custompurging with nitrogen
  5. customThe reaction mixture was partitioned between EtOAc and aqueous NH4OAc 25%
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography

Quellen und Nachweise

ORD-Eintrag
ord-fee9e09051764200bddded7fe9a43e63
Quelldatensatz
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07973037B2

Notizen zur Reaktion

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