2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 50939861, Verbindung

HRID 1618655Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1618655
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH2:15])[C:3]=1[CH3:22].[CH3:23][C:24]1([CH3:39])[C:28]2=[N:29][CH:30]=[C:31]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)[CH:32]=[C:27]2[NH:26][CH2:25]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:23][C:24]1([CH3:39])[C:28]2=[N:29][CH:30]=[C:31]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)[CH:32]=[C:27]2[N:26]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=3[F:12])[N:5]=[C:4]([C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH2:15])[C:3]=2[CH3:22])[CH2:25]1

Komponenten

7

Edukt 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholineHCID 67284590HCID 67284590, Verbindung

Produkt 1

HCID 50939861HCID 50939861, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

4-Chloro-5,7-difluoro-3-methyl-2-(1-phenylvinyl)quinoline (80 mg, 0.253 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (59.1 mg, 0.253 mmol), Pd2dba3 (23.2 mg, 0.025 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (24.2 mg, 0.051 mmol), sodium tert-butoxide (73.0 mg, 0.760 mmol), and toluene (2.53 mL) were stirred at 105° C. for 2 h. The reaction mixture was then concentrated and the resulting residue partitioned between EtOAc and saturated aqueous sodium bicarbonate solution. The organic layer was washed with brine and water, then dried (MgSO4) and concentrated. Purification by flash chromatography eluting with a gradient of 0-65% hexane in EtOAc gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(1-phenylethenyl)quinoline. 1H NMR (400 MHz, chloroform-d) δ ppm 7.72 (1H, m), 7.53 (1H, m), 7.28-7.33 (5H, m), 7.01 (1H, m), 6.02 (1H, d, J=0.8 Hz), 5.63 (1H, br. s.), 5.61 (1H, d, J=1.0 Hz), 3.87 (1H, m), 3.71-3.79 (4H, m), 3.61 (1H, m), 2.96 (4H, d, J=0.8 Hz), 2.02 (3H, s), 1.55 (6H, m). Mass Spectrum (ESI) m/e=513.2 (M+1).

Aufarbeitung

  1. concentrationThe reaction mixture was then concentrated
  2. customthe resulting residue partitioned between EtOAc and saturated aqueous sodium bicarbonate solution
  3. washThe organic layer was washed with brine and water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by flash chromatography
  7. washeluting with a gradient of 0-65% hexane in EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-b342e35eabf34de1a2cd26aece158966
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765940B2

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