Sodium Carbonate → N-(4'-Cyano-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

HRID 1660949Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1660949
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].[N:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[N:14]([C:21]2[CH:26]=[CH:25][C:24]([CH2:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34](I)=[C:33]([C:38]([F:41])([F:40])[F:39])[CH:32]=3)=[O:29])=[CH:23][CH:22]=2)[CH:13]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.CCOC(C)=O.O.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:1]([C:3]1[CH:8]=[CH:7][C:6]([C:34]2[C:33]([C:38]([F:39])([F:40])[F:41])=[CH:32][C:31]([NH:30][C:28](=[O:29])[CH2:27][C:24]3[CH:23]=[CH:22][C:21]([N:14]4[C:15]5=[N:16][CH:17]=[CH:18][CH:19]=[C:20]5[N:12]=[CH:13]4)=[CH:26][CH:25]=3)=[CH:36][CH:35]=2)=[CH:5][CH:4]=1)#[N:2]

Komponenten

9

Edukt 3

HCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 119935762-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4-iodo-3-trifluoromethyl-phenyl)-acetamide

Produkt 1

HCID 11993577N-(4'-Cyano-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 4-cyanophenylboronic acid (62 mg, 0.42 mmol, 2 equiv) in EtOH (0.2 mL) is added dropwise to a mixture of 2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4-iodo-3-trifluoromethyl-phenyl)-acetamide (Example 12) (110 mg, 0.21 mmol), PdCl2(dppf)2 (5 mg, 0.01 mmol, 0.03 equiv), Na2CO3 (2 M solution in H2O, 0.42 mL, 0.84 mmol, 4 equiv) in toluene (1 mL) at reflux. The reaction mixture is stirred at reflux for 1 h, allowed to cool to rt and diluted with EtOAc and H2O. The aqueous layer is separated and extracted twice with EtOAc. The combined organic phase is washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Silica gel column chromatography purification (CH2Cl2/MeOH, 96:4) provides the title compound as a white solid: ES-MS: 495.9 [M-H]−; single peak at tR=4.68 min (System 1); Rf=0.15 (CH2Cl2/MeOH, 96:4).

Aufarbeitung

  1. temperatureat reflux
  2. temperatureat reflux for 1 h
  3. customThe aqueous layer is separated
  4. extractionextracted twice with EtOAc
  5. washThe combined organic phase is washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customSilica gel column chromatography purification (CH2Cl2/MeOH, 96:4)

Quellen und Nachweise

ORD-Eintrag
ord-6168c1083e834184a75fc31f4925010e
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030311B2

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