N-methyl-2-pyrrolidone → 6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbonitrile

HRID 1691431

Reaktionsgleichung

Reaktionsgleichung von HRID 1691431
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:6]=2[CH:33]=1.[CH3:34][N:35]1C(=O)CCC1>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.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].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.[Fe+2]>[C:29]([C:26]1[CH:27]=[CH:28][C:23]([S:20]([N:7]2[C:6]3[CH:33]=[C:2]([C:34]#[N:35])[CH:3]=[CH:4][C:5]=3[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8]2)(=[O:22])=[O:21])=[CH:24][CH:25]=1)([CH3:32])([CH3:31])[CH3:30]

Komponenten

7

Edukt 2

HCID 13387N-methyl-2-pyrrolidoneHCID 59618636HCID 59618636, Verbindung2×

Produkt 1

HCID 669015676-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (0.860 g, 1.60 mmol, intermediate 53), zinc cyanide (0.112 g, 0.96 mmol), Pd2(dba)3 (0.293 g, 0.320 mmol), and dppf (0.443 g, 0.80 mmol) in NMP (6.5 mL) under nitrogen was stirred at rt for 0.5 h and at 100° C. overnight. After cooling to rt, the reaction mixture was diluted with EtOAc and filtered. The filtrate was washed with water (3×), brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography, eluting with mixtures of hexane and EtOAc, to provide the title compound. LC/MS: m/e 487.2 (M+H)+. NMR (500 MHz, CDCl3): δ 7.94 (1H, d, J=1.6 Hz), 7.66 (1H, d, J=7.5 Hz), 7.53 (1H, dd, J=8.4, 2.0 Hz), 7.19 (1H, d, J=7.3 Hz), 7.13 (2H, d, J=8.7 Hz), 7.04 (1H, s), 6.94 (2H, d, J=8.6 Hz), 6.83 (1H, d, J=8.5 Hz), 4.70-4.90 (2H, br), 1.26 (9H, s).

Aufarbeitung

  1. temperatureAfter cooling to rt
  2. filtrationfiltered
  3. washThe filtrate was washed with water (3×), brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography
  8. washeluting with mixtures of hexane and EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-55838610b2454205a139f7f8d0605236
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153626B2

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