Water → HCID 71736417, Verbindung

HRID 1471779

Reaktionsgleichung

Reaktionsgleichung von HRID 1471779
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[C:21](Cl)=[CH:20][N:19]=[C:18]([C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][C:24]=3[F:31])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-:32].[K+].C(P(C(C)(C)C)C1(C(C)C)CC(C(C)C)=CC(C(C)C)=C1C1C=CC=CC=1)(C)(C)C.[OH2:64]>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.C(Cl)(Cl)Cl.[Pd].[Pd].O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:64][C:21]3=[CH:20][N:19]=[C:18]([C:23]4[CH:28]=[CH:27][C:26]([C:29]([NH2:30])=[O:32])=[CH:25][C:24]=4[F:31])[CH:17]=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 962Water2×HCID 14797Potassium HydroxideHCID 668498352-DI-Tert-Butylphosphino-2,4,6-TriisopropylbiphenylHCID 86694573HCID 86694573, Verbindung

Produkt 1

HCID 71736417HCID 71736417, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A flask is charged under Ar atmosphere with a stir bar, 4-[5-chloro-2-(4-cyano-2-fluoro-phenyl)-pyridin-4-ylethynyl]-piperidine-1-carboxylic acid tert-butyl ester (110 mg), powdered KOH (42 mg), 2-di-tert-butylphosphino-2,4,6-triisopropylbiphenyl (8 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (6 mg), water (1.5 mL), and 1,4-dioxane (3 mL). The mixture is heated to 110° C. and stirred at this temperature for 2 h. After cooling the mixture to room temperature, water is added and the resulting mixture is extracted with ethyl acetate. The combined extracts are washed with brine, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel [dichloromethane/(dichloromethane/methanol/7 M ammonia in methanol 50:48:2) 9:1] to give the title compound. LC (method 3): tR=1.26 min; Mass spectrum (ESI+): m/z=440 [M+H]+.

Aufarbeitung

  1. additionA flask is charged under Ar atmosphere with a stir bar
  2. temperatureAfter cooling the mixture to room temperature
  3. extractionthe resulting mixture is extracted with ethyl acetate
  4. washThe combined extracts are washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel [dichloromethane/(dichloromethane/methanol/7 M ammonia in methanol 50:48:2) 9:1]

Quellen und Nachweise

ORD-Eintrag
ord-111f8376e6174daf84391cd7100ff4c5
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012456B2

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