Water → 5-Trimethylsilylethynyl-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridine

HRID 1845883Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1845883
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=2[Cl:19])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:20][Si:21]([C:24]#[CH:25])([CH3:23])[CH3:22].[CH2:26](N(CC)CC)C.O>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:20][Si:21]([C:24]#[C:25][C:2]1[CH:3]=[C:4]([O:9][CH:10]([C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=2[Cl:19])[CH3:26])[C:5]([NH2:8])=[N:6][CH:7]=1)([CH3:23])[CH3:22]

Komponenten

9

Edukt 4

HCID 962WaterHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 211114855-Bromo-3-(2,6-dichloro-3-fluoro-benzyloxy)-pyridin-2-ylamine

Produkt 1

HCID 1234568855-Trimethylsilylethynyl-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridineAusbeute 62,9 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11776TriphenylphosphineKatalysatorHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

5-bromo-3-(2,6-dichloro-3-fluoro-benzyloxy)-pyridine-2-amine (3.8 g, 10 mmol), trimethylsilylethyne (3.87 mL, 28 mmol), triethylamine (Et3N, 4.15 mL, 30 mmol), triphenylphosphine (PPh3, 52 mg, 0.2 mmol) and bis(triphenylphosphine)palladium dichloride (PdCl2(PPh3)2, 140.3 mg, 0.2 mmol) was dissolved in N,N-dimethyl formamide (DMF, 10 mL), to which argon gas was bubbled for 10 min, then CuI (19 mg, 0.1 mmol) was added, the resultant reaction liquid was stirred under heating at 90° C. After 4.5 h, the reaction liquid was cooled to room temperature, water (10 mL) was added to quench the reaction. The resultant mixture was extracted with ethyl acetate (3×20 mL), the organic phases were combined, washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated, the resultant residue was purified via silica gel column chromatography (PE/EA=3:1) to yield 2.5 g of the target product as brown solid.

Aufarbeitung

  1. customwas bubbled for 10 min
  2. customthe resultant reaction liquid
  3. customthe reaction liquid
  4. temperaturewas cooled to room temperature
  5. customto quench
  6. customthe reaction
  7. extractionThe resultant mixture was extracted with ethyl acetate (3×20 mL)
  8. washwashed with water and saturated brine successively
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customthe resultant residue was purified via silica gel column chromatography (PE/EA=3:1)

Quellen und Nachweise

ORD-Eintrag
ord-68ec179b49284b9f9b0ede08d7e23fc6
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952002B2

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