Triethylamine → 6-(((2S,4R)-1-Acetyl-2-methyl-6-((trimethylsilyl)ethynyl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

HRID 628953

Reaktionsgleichung

Reaktionsgleichung von HRID 628953
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[C@H:7]([NH:15][C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][N:17]=2)[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2].[C:25]([Si:27]([CH3:30])([CH3:29])[CH3:28])#[CH:26].C(N(CC)CC)C>CN(C=O)C.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>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:26]#[C:25][Si:27]([CH3:30])([CH3:29])[CH3:28])=[CH:11][CH:12]=2)[C@H:7]([NH:15][C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][N:17]=2)[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 709779596-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Produkt 1

HCID 709781736-(((2S,4R)-1-Acetyl-2-methyl-6-((trimethylsilyl)ethynyl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

6-(((2S,4R)-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 6) (1.62 g, 4.20 mmol), ethynyltrimethylsilane (17.5 ml, 124 mmol), triethylamine (23 ml, 165 mmol), bis(triphenylphosphine)palladium(II) chloride (0.590 g, 0.841 mmol) and copper(I) iodide (0.080 g, 0.420 mmol) were mixed in DMF (18 ml) and heated at 90° C. overnight. The reaction was concentrated in vacuo, diluted with water (30 ml), and extracted with DCM (3×30 ml). The organics were combined and dried (hydrophobic frit). The solution was concentrated in vacuo, and the residue purified by chromatography on a silica cartridge (100 g) eluting with an ethylacetate/cyclohexane gradient (0-75% over 14 CVs). The appropriate fractions were collected and the solvent evaporated in vacuo to give 6-(((2S,4R)-1-acetyl-2-methyl-6-((trimethylsilyl)ethynyl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (881 mg) as a black foam, which was used without further purification. LCMS (formate), Rt 1.24 min, MH+ 402

Aufarbeitung

  1. concentrationThe reaction was concentrated in vacuo
  2. additiondiluted with water (30 ml)
  3. extractionextracted with DCM (3×30 ml)
  4. customdried (hydrophobic frit)
  5. concentrationThe solution was concentrated in vacuo
  6. customthe residue purified by chromatography on a silica cartridge (100 g)
  7. washeluting with an ethylacetate/cyclohexane gradient (0-75% over 14 CVs)
  8. customThe appropriate fractions were collected
  9. customthe solvent evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-69727b98070145fabdcd6ce4f8f70de1
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315487B2

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